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US 20060018.933A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2006/0018933 A1 Vaya et al. (43) Pub. Date: Jan. 26, 2006

(54) NOVELDRUG DELIVERY SYSTEM (30) Foreign Application Priority Data Aug. 5, 2002 (IN)...... 698/MUM/2002 (76) Inventors: Navin Vaya, Gujarat (IN); Rajesh Aug. 5, 2002 (IN). ... 696/MUM/2003 Singh Karan, Gujarat (IN); Sunil Jan. 22, 2003 (IN)...... 81/MUM/2003 Sadanand Nadkarni, Gujarat (IN); Vinod Kumar Gupta, Gujarat (IN) Publication Classification (51) Int. Cl. Correspondence Address: A6IK 9/24 (2006.01) HEDMAN & COSTIGAN P.C. A6IK 9/00 (2006.01) 1185 AVENUE OF THE AMERICAS (52) U.S. Cl...... 424/400; 424/472 NEW YORK, NY 10036 (US) (57) ABSTRACT (21) Appl. No.: 11/134,631 A novel modified release dosage form comprising of a high (22) Filed: May 19, 2005 Solubility active ingredient, which utilizes dual retard tech nique to effectively reduce the quantity of release controlling Related U.S. Application Data agents. Present invention can optionally comprise addition ally another active ingredient as an immediate release form (63) Continuation-in-part of application No. 10/630,348, or modified release form. Present invention also relates to a filed on Jul. 29, 2003. process for preparing the Said formulation. Patent Application Publication Jan. 26, 2006 Sheet 1 of 5 US 2006/0018933 A1 FIGURE 1 (a)

FIGURE 1 (b)

Patent Application Publication Jan. 26, 2006 Sheet 2 of 5 US 2006/0018933 A1 FIGURE 2

12 O

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O ------O 2 4 6 8 O 12 4 16 18 2O 22 24 26 Time (hour) Patent Application Publication Jan. 26, 2006 Sheet 4 of 5 US 2006/0018933 A1

FIGURE 4

120

100 e

80

60

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- 1600 r 5G -- 1400 200 o 1000 - 800 gr 600 O 400 ? 200 H ?h

Tine Hours US 2006/OO18933 A1 Jan. 26, 2006

NOVELDRUG DELIVERY SYSTEM 0006. One method of prolonging the release of a highly water-soluble is disclosed PCT Patent application no. 0001. This application is a continuation-in-part of Ser. WO99/47128. Abiphasic controlled release delivery system No. 10/630,348, filed Jul. 29, 2003. for hydrochloride, which has prolonged gastric residence and that Swells following hydration. The ratio of FIELD OF INVENTION inner Solid phase to outer continuous phase is 0.5:1 to about 4:1. The major limitation of this invention is that it provides 0002 This invention relates to a modified release dosage a very bulky formulation for higher doses of the metformin form comprising of a high Solubility active ingredient, hydrochloride that is very inconvenient for human consump which utilizes dual retard technique to effectively reduce the tion. For instance, example cited provides formulation of quantity of release controlling agents. Present invention can 500 mg metformin hydrochloride with tablet weight of 1.0 optionally comprise additionally another active ingredient as gm. Hence restricting to the low dose Sustained release an immediate release form or modified release form. Present tablets of 500 mg or slightly more and making it obligatory invention also relates to a proceSS for preparing the Said to take two tablets of 500 mg each time to provide sustain formulation. action. The cited example teaches use of combination of atleast one hydrophilic polymer and which is a essential part BACKGROUND OF THE INVENTION for Swelling. Non Swellable or nonerodeble formulations are not included in the invention. 0003. It is well known to those skilled in the art that the 0007 PCT application No. WO 02/28181A1 describes a blood levels of need to be maintained above a mini monolithic Sustained release formulation of metformin mum effective level and below its minimum toxic level in hydrochloride. The method of making the formulation order to obtain the desired therapeutic effects and to mini involves hot melt granulation followed by wet granulation mize Side effects. Unfortunately, the pharmacokinetic prop with binders or extrusion. The formulation essentially erties (absorption, elimination and metabolism) of most requires binder and auxiliary pharmaceutically acceptable drugs are Such that they need to be administered three to four excipients. The formulation consists of metformin hydro times a day. This kind of a dosing regimen is very incon chloride polymer and or hydrophobic material. The dosage Venient and leads to reduction in patient compliance. Reduc form release more than 90% of the drug within 8 hours. tion of dosing regimen from three times a day (t.i.d.) to twice 0008 Similarly U.S. Pat. No. 6,340,475 B2 assigned to daily (b.i.d.) to once a day results in increased convenience Depomed Inc. describes monolithic controlled release for and comfort and therefore increased patient compliance. mulation of highly water Soluble drugs including metformin Drugs that are administered in the form of conventional hydrochloride. The formulation Swells when ingested thus tablets of capsules become available to body fluids at a rate prolonging its residence time in the Stomach. The formula that is initially very high, followed by a rapid decline. For tions are made of hydrophilic polymers, which results in many drugs, this delivery pattern results in a transient Swellable and erodible matrix. Overdose, followed by a long period of under dosing. This is a pattern of limited clinical usefulness. The delivery pattern 0009. Another method of prolonging the release of a was improved in the 1970's with the introduction of a highly water-Soluble drug is disclosed in International Patent variety of modified delivery systems. Modified release for application publication no. WO 96/26718, published Sep. 6, mulations, which are effective in maintaining the therapeutic 1996. The method of this publication is the incorporation of blood levels over, extended periods of time result in optimal the drug into a polymeric matrix to form a tablet that is therapy. They not only reduce the frequency of dosing, but administered orally. The polymer is water-swellable yet they also reduce the Severity and frequency of Side effects, erodible in gastric fluids. as they maintain Substantially constant blood levels and 0010 Similarly Chih-Ming Chen in international patent avoid the fluctuations associated with the conventional application number WO 02/36100 describes a once a for immediate release formulations administered three to four mulation of metformin hydrochloride which is based on times a day. oSmotically controlled technique and that is non expandable 0004. There are a number of different modified release in nature and has a passage in the coating membrane for dosage forms available commercially. However, Some of release of drug. these are expensive to manufacture and can be difficult to 0011 Kim et al. in U.S. Pat. No. 6,337,091 describes a Swallow, particularly in elderly patients. Many of these matrix based controlled release formulation for highly modified delivery Systems utilize hydrophilic, polymeric Soluble drugs over long periods of time. The release con matrices that provide useful levels of control to the delivery trolling agent is a Swellable gum which encapsulates or of sparingly Soluble drugs. For Soluble drugs, however, and make granules of drug, which is then disposed in more particularly for highly Soluble drugs, Such matrices do not Swellable erodible polymers such as HPMC or poly(ethyl provide adequate control over the release rate, instead result eneoxide). ing in a release that approximates first-order kinetics and may have a problem of dose dumping or burst release. 0012. These systems can provide for modified release for However, Since many modified release dosage forms contain Selected active ingredients like active ingredients with low comparatively large amounts of active ingredient it is often dose or low water solubility. However, when a highly necessary to include large amounts of Suitable excipients to Soluble or high dose active ingredient is used, most of these achieve appropriate controlled release profiles. Clearly, this Systems have the disadvantages Such as comparatively low will tend to increase the Size of the dosage form. payload of active ingredient thus making dosage form bulky and expensive or lead to burst effect or prolonged release of 0005 The various techniques to make modified release active ingredient for a shorter duration or use of complex dosage form of drugs as described in prior art are as follows manufacturing procedure and/or equipment. US 2006/OO18933 A1 Jan. 26, 2006

0013 There exists a need for compositions and process 0025 The present invention further provides a method of for making orally deliverable dosage form containing highly treating an animal, particularly a human in need of treatment Soluble active ingredient as modified release that overcomes utilizing the active agents, comprising administering a thera the problems discussed above. This invention addresses the peutically effective amount of composition or Solid oral need. dosage form according to the invention to provide admin istration of active ingredients. 0.014. Therefore, it would be of considerable clinical benefit to design a dosage form with high payload of highly DETAILED DESCRIPTION OF THE soluble active ingredient that would be much easier for the INVENTION patient to Swallow. This type of technology could also be used to reduce the size of many existing drug formulations. 0026. This invention relates to a modified release dosage form comprising of a high Solubility active ingredient pre 0.015 Therefore an object of the present invention is a pared by using dual retard technique to control the release of modified release dosage form of high Solubility active the high Solubility active ingredient and to increase the ingredient. payload of high Solubility active ingredient 0016. The second object of the present invention is a 0027. The term “modified release” as used herein in modified release dosage form with high payload of active relation to the composition according to the invention or a ingredient, which is Suitable for Swallowing for humans. rate controlling polymer or used in any other context means 0.017. Yet another object of the present invention is to release, which is not immediate release and is taken to provide a dosage form, which uses dual retard technique to encompass controlled release, Sustained release, prolonged control the release of the high Solubility active ingredient release, timed release, retarded release, extended release and and Significantly reduce the amount of release controlling delayed release. The term "modified release dosage form' as agents which are otherwise required in very high quantity used herein can be described as dosage forms whose drug and make the dosage form very bulky and therefore pose release characteristics of time course and/or location are difficulty in Swallowing. chosen to accomplish therapeutic or convenience objectives not offered by conventional dosage forms Such as a Solution 0.018. A further object of the present invention is to or an immediate release dosage form. Modified release Solid provide a dosage form, which gives accurate dosing and is oral dosage forms include both delayed and extended release Simple to prepare. drug products (as per US FDA guideline for SUPAC-MR: Modified Release Solid Oral Dosage Forms). 0.019 A further object of the present invention is to provide a dosage form, which can be given twice a day or 0028. The term “dosage form' denotes any form of the more preferably can be given once a day. formulation that contains an amount Sufficient to achieve a therapeutic effect with a single administration. 0020. A further object of the present invention is to 0029. The term “active ingredient” refers to an agent, provide a dosage form, which can optionally comprise active ingredient compound or other Substance, or compo additionally another active ingredient as an immediate Sitions and mixture thereof that provide Some pharmaco release form or modified release form. logical, often beneficial, effect. Reference to a specific active ingredient shall include where appropriate the active ingre SUMMARY OF THE INVENTION dient and it's pharmaceutically acceptable Salts. 0021. The above objects are realized by a dosage form, 0030 The term “high solubility” as used herein in rela which comprises of a) Micro matrix particles containing tion to active agent means that from less than 1 part to 300 high Solubility active ingredient and one or more hydropho parts of water or less than 1 part to 30 parts of water will be bic release controlling agent, b) Coating of Micro matrix required to dissolve 1 part of active ingredient. particles with one or more hydrophobic release controlling agents. It may optionally also include one or more com 0031. The invention provides a novel modified release monly used excipients in oral pharmaceutical formulations. dosage form of high Solubility active ingredient, which The present invention also provides Solid oral dosage form utilizes dual retard technique to effectively reduce the quan comprising a composition according to the invention. tity of release controlling agents and a process for preparing Optionally, it may also comprise additionally another active the dosage form. ingredient as an immediate release form or modified release 0032 The dosage form comprises of a) Micro matrix form. particles containing, high Solubility active ingredient and one or more hydrophobic release controlling agent, b) Coat 0022. The present invention also teaches the use of dual ing of Micro matrix particles with one or more hydrophobic retard technique to effectively control the release rate of release controlling agents. It may optionally also include one modified release active ingredient by using Small quantity of or more commonly used excipients in oral pharmaceutical release controlling agents. This dual retard technique thus formulations. The release of high Solubility active ingredient Sufficiently reduces the Size of the dosage form, which is is controlled through dual retard technique. The dual retard convenient for Swallowing. technique is a combination of matrix formulations and 0023 The present invention further teaches the use of reservoir formulations. First the micromatrix particles of hydrophobic release controlling agents. high Solubility dose active ingredient and one or more hydrophobic release controlling agents are formed and then 0024. The present invention also provides a novel process these are further coated with one or more release controlling for preparing the novel formulations of the invention. agents. Thus the dual retard release technique presents the US 2006/OO18933 A1 Jan. 26, 2006

double barriers and effectively controls the diffusion of the nogen activator, platelet activating factor antagonist, platelet high Solubility active ingredients from the present invention aggregation inhibitor, psychotropic, radioactive agent; in predictable manner and also significantly reduces the Scabicide, Sclerosing agent, , Sedative-, amount of release controlling agents which are otherwise Selective Al antagonist; antagonist; required in very high quantity and make the dosage form Serotonin inhibitor, Serotonin ; ; very bulky and therefore pose difficulty in Swallowing. The thyroid hormone; thyroid inhibitor; thyromimetic, tranquil other advantages of the present invention are Such as it izer, amyotrophic lateral Sclerosis agent, cerebral ischemia reduces the chances of dose dumping, unnecessary burst agent, Paget's disease agent; unstable angina agent; VaSO effects and failure of the System, which are otherwise usually constrictor; vasodilator, wound healing agent; oxi asSociated with simple matrix or reservoir Systems. dase inhibitor. 0033) Optionally, it may also contain another active 0037 Examples of high solubility active ingredients ingredient as an immediate release form or modified release comprises of but not limited to Abacavir Sulfate; Aminoca form. proic acid; Alendronate Sodium; hydrochlo ride, , Acetaminophen; Sulfate; Bal 0034. The high solubility active ingredient can be present Salazide, BenZepril hydrochloride, fumarate; in the form of a free base or in the form of pharmaceutically hydrochloride; Buformin; Captopril; Cetrizine acceptable Salts. Pharmaceutically acceptable Salts forming hydrochloride; Ciprofloxacin; Clindamycin; Chlorphe part of this invention are intended to define but not limited niramine maleate; hydrochloride; Clomi to Salts of the carboxylic acid moiety Such as alkali metal pramine hydrochloride; hydrochloride; Clopi Salts like Li, Na and K Salts, alkaline earth metal Salts like dogrel bisulfate; Cloxacillin Sodium, Codeine phosphate; Ca and Mg Salts, Salts of organic baseS Such as , Colchicines, Cyclophosphamide; Diethylcarbamazine cit arginine, , diethanolamine, choline, and the like; rate; DL-methionine; Eprosartan; Ethembutol hydrochlo ammonium or Substituted ammonium Salts and ride; ; ; Ferrous sulfate; Fluox salts. Salts may be acid addition salts which defines but not etine hydrochloride; Fosinopril Sodium; ; limited to Sulfates, nitrates, phosphates, perchlorates, Hydralazine hydrochloride; Hydrocodone bitartrate; borates, hydrohalides, , tartrates, maleates, citrates, hydrochloride; Hydroxyurea; Indinavir Sul Succinates, palmoates, methaneSulfonates, benzoates, Sali fate; , ISOSorbide moninitrate, Lactobionate; Lami cylates, hydroxynaphthoates, benzenSulfonates, ascorbates, Vudine; Levamisole hydrochloride; Levofloxacin; Lisino glycerophosphates, ketoglutarates and the like. pril; Losartan potassium; Metformin hydrochloride; 0035) Further, high solubility active ingredient, where hydrochloride; tartrate; applicable, may be present either in the form of one Sub Minocycline hydrochloride; Montelukast sodium; Naproxen Stantially optically pure enantiomer or as a mixture of Sodium; Neostigmine ; ; ; enantiomers or polymorphs thereof. Nifurtimox; hydrochloride; Olanzepine; Oxy bytynin chloride; Penicillamine; Penicillin V potassium; 0.036 The high solubility active ingredients comprises of sodium; Phenformin; Pravastatin sodium; Potas the following therapeutic classes but not limited to adren sium chloride; Primaquine phosphate, ; ergic agent, adrenocortical Steroid; adrenocortical Suppres Promethazine hydrochloride; Proponolol hydrochloride; Sant; antagonist, amino acid; anabolic; analep Propoxyphene hydrochloride; Pseudophedrine hydrochlo tic; analgesic, anesthetic, , anti-acne agent, anti ride; Pyridostigmine bromide; Pyridoxine hydrochloride; , anti-allergic, anti-amebic, anti-anemic, anti Quinapril hydrochloride, , Ramipril; anginal; anti-arthritic, anti-asthmatic, anti-atherOSclerotic, hydrochloride; Risedronate Sodium; RosiglitaZone maleate; antibacterial; anticholinergic, anticoagulant; , Sodium ; sulfate; Stavudine; Sumatrip , antidiabetic, antidiarrheal; antidiuretic, anti tan Succinate, hydrochloride; Tetracycline hydro emetic, anti-epileptic, antifibrinolytic, antifungal; antihem chloride; meleate; Tramodol hydrochloride; Vala orrhagic, , antihyperlipidemia; antihyperten cyclovir hydrochloride; Vancomycin; Sive, antihypotensive; anti-infective, anti-inflammatory; hydrochloride; acetylsalicylic acid, acyclovir; allopurinol, antimicrobial; antimigraine; antimitotic, antimycotic, antin beSylate; amoxicillin; , atorvastatin cal auseant, antineoplastic, antineutropenic, antiparasitic; anti cium; azithromycin; carbidopa; , cefprozil; proliferative; , antirheumatic, antiseborrheic, celecoxib, cephalaxin, , hydrobro antisecretory; antispasmodic, antithrombotic, anti-ulcer mide; clindamycin hydrochloride, hydro ative; antiviral; appetite Suppressant, blood glucose regula chloride; desloratidine, meSylate, doxycycline; tor, bone resorption inhibitor; bronchodilator; cardiovascu enalapril maleate; , hydrochloride; lar agent, cholinergic, depressant, diagnostic aid; , fluconazole, folic acid; irbesartan; levodopa; ; agent; estrogen receptor , fibrinolytic, Sodium, , hydrochloride; fluorescent agent, free oxygen radical Scavenger; gastric , metronidazole, mirtazepine, nitrofurantoin, acid SupreSSant; gastrointestinal motility effector; glucocor nyStatin, hydrochloride, paracetamol, ticoid; hair growth , hemostatic; H2 hydrochloride; quetiapine fumerate, ralox receptor antagonists, hormone; hypocholesterolemic, ifene, hydrochloride; ; hydrochloride; hypoglycemic, hypolipidemic, hypotensive; imaging agent; Sildenafil citrate, Simvastatin; tamoxifen citrate; immunizing agent, immunomodulator; immunoregulator; hydrochloride; , tartrate; ; immunostimulant; immunosuppressant, keratolytic, LHRH hydrochloride; trimethoprim; Valsartan; agonist, mood regulator, mucolytic, mydriatic, nasal decon tartrate; hydrochloride; Wafarin Sodium and the gestant; neuromuscular blocking agent; neuroprotective; active ingredients described in U.S. Pat. Nos. 2,968,158, NMDA antagonist; non-hormonal sterol derivative; plasmi 3,097,242, 3,454,635, 3,654,357, 3,668,215, 3,669,966, US 2006/OO18933 A1 Jan. 26, 2006

3,708,486, 3,801,495, 5,104,888, 5,232,945, 5,264,451, (butyl methacrylate), poly(isobutyl methacrylate), and poly 5,478,852, 6,296,874, 3,957,853, 4,080.472, 3,174,901, (hexyl methacrylate). Poly(isodecyl methacrylate), poly 4,835,184, 6,031,004 and European patent publication num (lauryl methacrylate), poly(phenyl methacrylate), bers EP0008203, EP0032128, EPO139421, EPO155845, poly(methyl acrylate), poly(isopropyl acrylate), poly(isobu EPO177353, EP0208420, EP0257881, EP0306228, tyl actylate), poly(octadecyl acrylate), waxes Such as bees EPO319189, EP0332331, EP0332332, EP0428312, wax, carnauba wax, microcrystalline wax, and OZokerite; EP0489663, EP0508740, EP0528734, EP0533933, fatty Such as cetoStearyl , Stearyl alcohol, EP0833933, EP87112480.6 and Japanese patent number cetyl alcohol and myristyl alcohol; and fatty acid esterS Such 05271204 and United Kingdom patent numbers 5504078, as glyceryl monoStearate, glyceryl distearate, glycerol GB2088365A and PCT patent application numbers WO91/ monooleate, acetylated monoglycerides, tristearin, tripalm 19702, WO92/03425, WO92/18501, WO93/02079, WO93/ itin, cetyl esters wax, glyceryl palmitoStearate, glyceryl 21166, WO93/22445, WO94/01420, WO94/05659. behenate, and hydrogenated castor oil. 0.038. The quantity of thehigh solubility active ingredient 0048. According to an especially preferred embodiment for e.g. as mentioned above can be less than or equal to 1500 the release controlling agent contains ammonio methacry mg. late co-polymers and fatty acid esters as hereinafter 0.039 Adosage form of the present invention may option described. ally contain more than one high Solubility active ingredient. 0049. The suitable hydrophobic agents are polymers sold under the Trade Mark Eudragit RS (Ammonio Methacrylate 0040 Adosage form of the present invention may option Copolymer type B USP).Eudragit NE 30D (Polyacrylate ally contain more than one antidiabetic active ingredient. dispersion 30% Ph., Eur), Eudragit RL (Ammonio Meth 0041 AS indicated above the outer portion of the present acrylate Copolymer type AUSP) and Kollicoat SR 30 Dand invention may comprise auxiliary excipients Such as for fatty acid esterS Such as glyceryl behenate, and hydrogenated example lubricants, plasticisers, anti-tack agents, opacifying castor oil. Eudragit polymers are polymeric lacquer Sub agents, pigments, and Such like. AS will be appreciated by stances based on acrylate and/or methacrylates. those skilled in the art, the exact choice of excipient and their 0050. The dosage form can also include one or more relative amounts will depend to Some extent on the final oral commonly used excipients in oral pharmaceutical formula dosage form. tions. 0.042 Suitable lubricants, including agents that act on the 0051 Representative commonly used excipients in oral flowability of the powder to be compressed are, for example, pharmaceutical formulations include talc, fumed Silica, colloidal slilcon dioxide such as Aerosil 200 (Aerosil is a glyceryl monoStearate, Stearate, Stear Trade Mark), talc, Stearic acid, magnesium Stearate, calcium ate, kaolin, colloidal Silica, gypsum, Tween 80, Geleol Stearate and Sodium Stearyl fumarate. pastiles (trade mark), micronised silica and magnesium 0043. In micro matrix particles, the active ingredient and trisilicate. one or more hydrophobic release controlling agents are 0052 The quantity of commonly used excipients in oral preferably present in a ratio of from 100:1 to 100:75, more pharmaceutical formulations used is from about 2% to about particularly from 100:2.5 to 100:50, still more preferably 500% by weight, preferably from 2 to 100% more particu from 100:2.5 to 100:30 and most preferably from 100:2.5 to larly 10 to 60% based on the total dry weight of the polymer. 100:2O. 0053. The dosage form can also include a material that 0044) Micro matrix particles and coating of one or more improves the processing of the release controlling agents. hydrophobic release controlling agents are preferably Such materials are generally referred to as "plasticisers' and present in a ratio of from 100:0.5 to 100:75, more particu include, for example, adipates, azelates, benzoates, citrates, larly from 100:2.5 to 100:50, still more preferably isoebucaes, phthalates, Sebacates, Stearates, tartrates, poly from 100:2.5 to 100:30 and most preferably from 100:2.5 to hydric alcohols and glycols. 100:2O. 0054 Representative plasticisers include acetylated 0.045 According to one embodiment the release control monoglycerides, butyl phthalylbutyl gylcolate, dibutyl tar ling agents are pharmaceutically excipients, which are trate; diethyl phthalate; dimethyl phthalate, ethyl phthalyl hydrophobic in nature. ethyl glycolate, glycerin; glycol, propylene glycol, Triethyl citrate, triacetin; tripropinoin, diacetin, dibutyl 0046) The polymers that can be used to form the rate phthalate; acetyl monoglyceride; polyethylene glycols, cas controlling membrane or micromatrix are described in tor oil; triethyl citrate; polyhydric alcohols, esters, greater detail herein below. glycerol triacetate, acetyl triethylcitrate, dibenzyl phthalate, 0047 The hydrophobic release controlling agents are dihexyl phthalate, butyl octyl phthalate, disononyl phtha Selected from but are not limited to Ammonio methacrylate late, butyloctyl phthalate, dioctyl azelate, epoxidised tallate, copolymers type A and B as described in USP, methacrylic triisoctyl trimellitate, diethyleXyl phthalate, di-n-octyl acid copolymer type A, B and C as described in USP phthalate, di-I-Octyl phthalate, di-I-decyl phthalate, di-n- Polyacrylate dispersion 30% as described in Ph. Eur, Poly undecyl phthalate, di-n-tridecyl phthalate, tri-2-ethyleXyl Vinyl acetate dispersion, ethylcellulose, cellulose acetate, trimelitate, di-2-ethyleXyl adipate, di-2-ethylhexyl Seba cellulose propionate (lower, medium or higher molecular cate, di-2-ethylhexyl azelate, dibutyl Sebacate, glyceryl weight), cellulose acetate propionate, cellulose acetate monocaprylate, glycerol distearate, glyceryl monocaprate, butyrate, cellulose acetate phthalate, cellulose triacetate, , oxybutamine chloride, perinodopril erbumine, poly(methyl methacrylate), poly(ethyl methacrylate), poly pilocorpine, poldine methyl Sulfate and Zalcitane. US 2006/OO18933 A1 Jan. 26, 2006

0.055 The amount of plasticiser to be used is from about platelet activating factor antagonist, platelet aggregation 1% to 50% based on the weight of the dry release controlling inhibitor, psychotropic, radioactive agent, Scabicide, Scle agent(s). rosing agent, Sedative, Sedative-hypnotic, Selective adenos ine Al antagonist; Serotonin antagonist, Serotonin inhibitor; 0056 The amount of release controlling agent(s) to be Serotonin receptor antagonist; Steroid; thyroid hormone; used in forming the outer portion will be determined based thyroid inhibitor; thyromimetic, tranquilizer; amyotrophic on various parameterS Such as the desired delivery proper lateral Sclerosis agent; cerebral ischemia agent, Paget's ties, including the amount of active ingredient to be deliv disease agent; unstable angina agent; vasoconstrictor; ered, the active ingredient release rate desired, and the size vasodilator, wound healing agent; Xanthine oxidase inhibi of the micro matrix particles. tor. 0057 Part comprising another active ingredient-It com 0061 Examples of active ingredient comprises of but not prises of active ingredient(s) and includes one or more limited to-16-alpha fluorocStradiol, 16alpha-gitoxin, commonly used excipients in oral immediate release or 16-epieStriol, 17 alpha dihydroequilenin, 17 alpha , modified release pharmaceutical formulations. 17 beta estradiol, 17 hydroxy , 1alpha-hydrox 0.058 The active ingredient(s) can be present in the form yvitamin D2, 1-dodecpyrrolidinone, 20-epi-1,25dihydrox of a free base or in the form of pharmaceutically acceptable yvitamin D3, 22-oxacalcitriol, 2CVV, 2'-nor-cGMP, Salts. Pharmaceutically acceptable Salts forming part of this 3-isobutyl GABA, 5-ethynyluracil, 6-FUDCA, 7-methox invention are intended to define but not limited to salts of the ytacrine, Abamectin, , , abiraterone, carboxylic acid moiety Such as alkali metal Salts like Li, Na Ablukast, Ablukast Sodium, Acadesine, acamprosate, Acar and K Salts, alkaline earth metal Salts like Ca and Mg Salts; bose, , Acecainide Hydrochloride, Aceclidine, Salts of organic baseS Such as lysine, arginine, guanidine, aceclofenae, AcedapSone, Aluminum, Ace diethanolamine, choline, and the like, ammonium or Substi mannan, Acetaminophen, Acetazolamide, , tuted ammonium Salts and aluminium Salts. Salts may be Acetohydroxamic Acid, acetomepregenol, acid addition salts which defines but not limited to Sulfates, Maleate, Acetosulfone Sodium, Chloride, nitrates, phosphates, perchlorates, borates, hydrohalides, Acetylcysteine, acetyl-L-carnitine, acetylmethadol, Acifran, acetates, tartrates, maleates, citrates, Succinates, palmoates, acipimox, acitemate, Acitretin, Acivicin, Aclarubicin, acla methaneSulfonates, benzoates, Salicylates, hydroxynaph tonium, Acodazole Hydrochloride, aconiazide, Acrisorcin, thoates, benzenSulfonates, ascorbates, glycerophosphates, , Acronine, Actisomide, Actodigin, Acyclovir, ketoglutarates and the like. acylfulvene, adafenoxate, adapalene, Adapalene, ada tanserin, Hydrochloride, adecypenol, adecype 0059 Further, active ingredient(s), where applicable, nol, Adefovir, adelmidrol, ademetionine, Adenosine, Adina may be present either in the form of one Substantially Zolam, Adipheinine Hydrochloride, adiposin, Adozelesin, optically pure enantiomer or as a mixture of enantiomers or , Adrenalone, airbutamine, alacepril, Alamecin, Ala polymorphs thereof. nine, Alaproclate, alaptide, Albendazole, albolabrin, 0060. The active ingredient(s) comprises of the following Albuterol, Albutoin, Alclofenae, AlclometaSone Dipropi therapeutic classes but not limited to adrenergic agent; onate, Alcloxa, aldecalmycin, Aldesleukin, Aldioxa, Alen adrenocortical Steroid; adrenocortical SuppreSSant; aldoster dronate Sodium, alendronic acid, , Alentemol one antagonist, amino acid; anabolic; analeptic; analgesic; Hydrobromide, Aletamine Hydrochloride, Aleuronium anesthetic, anorectic, anti-acne agent, anti-adrenergic, anti Chloride, Alexidine, alfacalcidol, Hydrochloride, allergic, anti-amebic, anti-anemic, anti-anginal; anti-ar , Acetonide, alglucerase, , ali thritic, anti-asthmatic, anti-atherosclerotic, antibacterial; nastine, Alipamide, Allantoin, , Allopurinol, anticholinergic, anticoagulant; anticonvulsant, antidepres ALL-TK antagonists, Alonimid, , Alosetron Sant; antidiabetic, antidiarrheal; antidiuretic, anti-emetic, Hydrochloride, AloVudine, Alpertine, Alpha Amylase, alpha anti-epileptic, antifibrinolytic, antifungal; antihemorrhagic; idoSone, , , Hydrochloride, antihistamine; antihyperlipidemia; antihypertensive, antihy AlprenoXime Hydrochloride, AlproStadil, Alrestatin potensive; anti-infective; anti-inflammatory; antimicrobial; Sodium, Tartrate, Alteplase, Althiazide, Altre antimigraine; antimitotic, antimycotic, antinauSeant, antine tamine, altromycin B, Alverinc Citrate, Alvircept Sudotox, oplastic, antineutropenic, antiparasitic, antiproliferative; Acetate, Hydrochloride, ambamus antipsychotic, antirheumatic, antiseborrheic, antisecretory; tine, Ambomycin, Ambruticin, Ambuphylline, AmbuSide, antispasmodic, antithrombotic, anti-ulcerative; antiviral; Amcinafal, Amcinonide, Amdinocillin, Amdinocillin Piv appetite SuppreSSant; blood glucose regulator, bone resorp oxil, Amedalin Hydrochloride, amelometasone, Ameltolide, tion inhibitor, bronchodilator; cardiovascular agent, cholin , Ametantrone Acetate, ameZinium metilsulfate, ergic, depressant, diagnostic aid; diuretic, dopaminergic amfebutamone, Amfenac Sodium, Amflutizole, Amicycline, agent; estrogen receptor agonist, fibrinolytic, fluorescent MeSylate, amidox, Amifloxacin, amifostine, agent, free oxygen radical Scavenger; gastric acid Supres Amikacin, Hydrochloride, Aminacrine Hydro Sant; gastrointestinal motility effector; glucocorticoid; hair chloride, Aminobenzoate Potassium, Aminobenzoate growth Stimulant; hemoStatic; Sodium, Aminocaproic Acid, Aminoglutethimide, Amino antagonists, hormone, hypocholesterolemic, hypoglycemic, hippurate Sodium, aminolevulinic acid, , hypolipidemic, hypotensive; imaging agent, immunizing , AminoSalicylate Sodium, AminoSalicylic acid, agent; immunomodulator; immunoregulator; immunostimu , Amiprilose Hydrochloride, Amiquinsin lant; immunosuppreSSant; keratolytic, LHRH agonist; mood Hydrochloride, , , Amitriptyline Hydro regulator, mucolytic, mydriatic, nasal decongestant; neuro chloride, AmlexanoX, amlodipine, Sodium, muscular blocking agent; neuroprotective; NMDA antago Amodiacquine, Amodiaquine Hydrochloride, Amorolfine, nist; non-hormonal Sterol derivative, plasminogen activator; , Amoxicillin, Amphecloral, Amphetamine Sul US 2006/OO18933 A1 Jan. 26, 2006

fate, Amphomycin, Amphotericin B, Ampicillin, ampiroxi , Betaxolol Hydrochloride, Bethanechol Chloride, cam, AmpyZine Sulfate, Amquinate, Amrinone, amrinone, Sulfate, betulinic acid, , Bevantolol amrubicin, Amsacrine, amylin, amythiamicin, Hydrochloride, Bezafibrate, bFGF inhibitor, Bialamicol Acetate, anagrelide, Anakinra, ananain, anaritide, Anaritide Hydrochloride, Biapenem, , Biciifadine Hydro Acetate, Anastrozole, Anazolene Sodium, Ancrod, androgra chloride, Biclodil Hydrochloride, Bidisomide, , pholide, , angiogenesis inhibitors, Angio Bifonazole, bimakalim, bimithil, Bindarit, Biniramycin, tensin Amide, Anidoxime, , Anilopam Hydro , bioxalomycin alpha2, Bipenamol Hydrochlo chloride, Aniracetam, Anirolac, Anisotropine ride, Biperiden, Biphenamine Hydrochloride, biriperone, Methylbromide, Anistreplase, AnitraZafen, anordrin, bisantrene, bisaramil, bisaZiridinylspermine, bis-benzimida antagonist D, antagonist G, antarelix, Phosphate, Zole A, bis-benzimidazole B, bisnafide, Bisobrin Lactate, Anthelmycin, Anthralin, , , Bisoprolol, Bispyrithione Magsulfex, bistramide D, bistra AcedapSone, , antieStrogen, antineoplaston, Anti mide K, bistratene A, Bithionolate Sodium, Mesy pyrine, antisense oligonucleotides, apadoline, apafant, Apal late, Bivalirudin, Bizelesin, Bleomycin Sulfate, cillin Sodium, apaxifylline, ApaZone, aphidicolin glycinate, Dipropionate, , Undecylenate, bol Apixifylline, Hydrochloride, , dine, , , , , Boxi Apraclonidine Hydrochloride, Apramycin, , dine, brefeldin, breflate, Brequinar Sodium, , Aprindine Hydrochloride, aproSulate Sodium, Aprotinin, Tosylate, Brifentanil Hydrochloride, brimoni Maleate, aptiganel, apurinic acid, apurinic acid, dine, Brinolase, Brocresine, Brocrinat, Brofoxine, Broma , Aranotin, Arbaprostil, arbekicin, arbidol, Arb doline Maleate, , Bromchlorenone, Brome utamine Hydrochloride, Arclofenin, Ardeparin Sodium, lains, bromfenac, Brominidione, , argatroban, Arginine, Argipressin Tannate, Arildone, arip Bromodiphenhydramine Hydrochloride, Bromoxanide, Bro iprazol, , Arpinocid, Arteflene, Artilide Fumarate, mperidol, Decanoate, Male asimadoline, aspalatone, Asparaginase, Aspartic Acid, ate, Broperamole, Bropirimine, , Bucainide ASpartocin, asperfuran, , aspoxicillin, Asprelin, Maleate, , Hydrochloride, Bucromar , Astromicin Sulfate, asulacrine, , one, BudeSonide, budipine, budotitane, Buformin, Bumet Atenolol, ate Virdine, , Maleate, anide, Bunaprolast, , Bunolol Hydrochloride, Atolide, Atorvastatin Calcium, Atosiban, Atovaquone, atpe Bupicomide, Hydrochloride, nin B, Atracurium BeSylate, atrimustine, atrinositol, Atro Hydrochloride, Bupropion Hydrochloride, Buramate, pine, Auranofin, aureobasidin A, Aurothioglucose, Avilamy Buserelin Acetate, Hydrochloride, Busulfan, But cin, Avoparcin, Avridine, AXid, axinastatin 1, axinastatin 2, abarbital, Butacetin, Hydrochloride, , axinastatin 3, AZabon, AZacitidinie, AZaclorZine Hydrochlo , Butamirate Citrate, , Butaprost, ride, AZaconazole, azadirachtine, AZalanstat Dihydrochlo Butedronate Tetrasodium, butenafine, Buterizine, buthion ride, AZaloxan Fumarate, AZanator Maleate, AZanidazole, ine Sulfoximine, Butikacin, Butilfenin, Butirosin Sulfate, , AZaribine, AZaserine, aZasetron, Butixirate, butiXocort propionate, Butoconazole Nitrate, Maleate, AZathioprine, AZathioprine Sodium, azatoxin, Butonate, Butopamine, Butoprozine Hydrochloride, Butor aZatyrosine, , , , AZepin phanol, Butoxamine Hydrochloride, Hydro dole, AZetepa, , Azithromycin, AZlocillin, chloride, Cactinomycin, CadeXomer Iodine, , cal AZOlimine, AZOSemide, AZotomycin, Aztreonam, anolide A, Calcifediol, Calcipotriene, calcipotriol, AZumolene Sodium, Bacampicillin Hydrochloride, baccatin Calcitonin, Calcitriol, Calcium Undecylenate, calphostin C, III, Bacitracin, , bacoside A, bacoside B, bactobo , Cambendazole, camonagrel, camptothecin lamine, balanol, balaZipone, balhimycin, balofloxacin, bal derivatives, canarypox IL-2, candesartan, Candicidin, can Salazide, Bambermycins, , Sulfate, doXatril, candoxatrilat, Caniglibose, Canrenoate Potassium, Bamifylline Hydrochloride, Bamnidazole, baohuoside 1, , capecitabine, Capobenate Sodium, Capobenic Barmastine, , Basifungin, Hydro Acid, Capreomycin Sulfate, capromab, capsaicin, Captopril, chloride, batebulast, Maleate, Batimastat, beau Capuride, Caracemide, , Carbadox, Carbam vericin, Becanthone Hydrochloride, becaplermin, beclicona azepine, Carbamide Peroxide, Carbantel Lauryl Sulfate, Zole, Beclomethasone Dipropionate, befloxatone, Carbaspirin Calcium, CarbaZeran, carbazomycin C, Carbe Beinserazide, Belfosdil, Belladonna, Beloxamide, nicillin Potassium, Carbenoxolone Sodium, Carbetimer, car , Bemitradine, Bemoradan, Benapry Zine Hydro betocin, Carbidopa, Carbidopa-Levodopa, chloride, Benazepril Hydrochloride, Benazeprilat, Benda Maleate, Carbiphene Hydrochloride, Carbocloral, Car calol Mesylate, Bendazac, Bendroflumethiazide, benflume bocysteine, Carbol-Fuchsin, Carboplatin, Carboprost, car tol, , , Benoxaprofen, Benoxaprofen, bovir, carboxamide-amino-triaZO-le, , Benoximate Hydrochloride, , , Ben carboxymethylated beta-1,3-glucan, Hydrochlo tiromide, Benurestat, Benzbromarone, Benzethonium Chlo ride, CaRest M3, Carfentanil Citrate, Carisoprodol, Carman ride, Benzetimide Hydrochloride, Benzilonium Bromide, tadine, Carmustine, CARN 700, Carnidazole, , BenZindopyrine Hydrochloride, benzisoxazole, , carperitide, Carphenazine Maleate, Carprofen, CarSatrin benzochlorins, Hydrochloride, BenZOdepa, Succinate, , , Carteolol Hydrochloride, benzoidaZOXan, BenZonatate, Benzoyl Peroxide, Ben cartilage derived inhibitor, Carubicin Hydrochloride, Caru Zoylpas Calcium, benzoylstauroSporine, , monam Sodium, , carvotroline, Carvotroline Benzthiazide, benztropine, Benztropine MeSylate, Benzy Hydrochloride, carzelesin, casein kinase inhibitors (ICOS), damine Hydrochloride, Benzylpenicilloyl Polylysine, bepri castanospermine, caurumonam, cebaracetam, cecropin B, dil, Hydrochloride, Beractant, Beraprost, , Cedefingol, Cefaclor, Cefadroxil, Cefamandole, Cefaparole, berlafenone, bertosamil, Berythromycin, besipirdine, beta Cefatrizine, Cefazaflur Sodium, Cefazolin, Cefbuperazone, alethine, betaclamycin B, Betamethasone, betamipron, cefcapene pivoxil, cefdaloxime penteXil tosilate, Cefdinir, US 2006/OO18933 A1 Jan. 26, 2006 cefditoren pivoxil, Cefepime, cefetamet, Cefetecol, conagenin, Conorphone Hydrochloride, contignasterol, con cefixime, cefluprenam, CefnmenoXime Hydrochloride, tortrostatin, Cormethasone Acetate, Corticorelin Ovine Tri Cefnmetazole, cefminlox, cefodizime, Cefonicid Sodium, flutate, Corticotropin, Acetate, CortivaZol, Corto CefoperaZone Sodium, Ceforanide, cefoSelis, Cefotaxime doxone, coSalane, costatolide, CoSyntropin, , Sodium, Cefotetan, cefotiam, CefoXitin, cefoZopran, cefpi Coumadin, Coumermycin, crambescidin 816, Crilvastatin, mizole, Cefpiramide, cefpirome, cefpodoxime proxetil, cef crisinatol, Cromitrile Sodium, Cromolyn Sodium, Crotami prozil, CefroXadine, cefSulodin, Ceftazidime, cefteram, cef ton, cryptophycin 8, cucumariosid, Cuprimyxin, curacin A, tibuten, Ceftizoxime Sodium, ceftriaxone, Cefuroxime, curdlan Sulfate, curiosin, Cyclacillin, Cyclazocine, cycla celastrol, celikalim, , cepacidine A, Cephacetrile Zosin, cyclic HPMPC, Cyclindole, Cycliramine Maleate, Sodium, Cephalexin, Cephaloglycin, Cephaloridine, Cepha , Cyclobendazole, cyclobenzaprine, cyclobut A, lothin Sodium, Cephapirin Sodium, Cephradine, cer cyclobut G, cyclocapron, Cycloquanil Pamoate, Cyclohex iclamine, cerivastatin, Ceronapril, certoparin Sodium, Ceru imide, cyclopentanthraquinones, Cyclopenthiazide, Cyclo letide, Cetaben Sodium, Cetalkonium Chloride, pentolate Hydrochloride, Cyclophenazine Hydrochloride, Hydrochloride, , , Cetophenicol, Cetraxate Cyclophosphamide, cycloplatam, , CycloS Hydrochloride, cetrorelix, Cetylpyridinium Chloride, erine, cycloSin, Cyclosporine, cyclothialidine, Cyclothiaz Chenodiol, Chlophedianol Hydrochloride, Betaine, ide, cyclothiazomycin, Cyheptamide, cypemycin, Cype Chlorambucil, Chloramphenicol, Chlordantoin, Chlordiaz namine Hydrochloride, , epoxide, Chlorhexidine Gluconate, chlorins, Hydrochloride, Cyprolidol Hydrochloride, , Acetate, chloroorienticin A, Hydrochloride, Cyproximide, CySteamine, Cysteine Hydrochloride, Cys Chloropropamide, Chloroquine, chloroquinoxaline Sulfona tine, Cytarabine, Cytarabine Hydrochloride, cytarabine mide, Chlorothiazide, Chlorotrianisene, Chloroxine, ocfoSfate, cytochalasin B, cytolytic factor, cytostatin, Dac Chloroxylenol, Chlorphenesin , Chlorphe arbazine, dacliximab, dactimicin, Dactinomycin, daidzein, niramine Maleate, Chlorpromazine, , Chlo Daledalin Tosylate, dalfopristin, Dalteparin Sodium, Dal rprothixene, Chlortetracycline Bisulfate, Chlorthalidone, troban, Dalvastatin, danaparoid, , Dantrolene, , Cholestyramine Resin, Chromonar Hydro daphlnodorin A, , dapitant, Dapoxetine Hydro chloride, cibenzoline, cicaprost, Hydrochloride, chloride, DapSone, Daptomycin, DarglitaZone Sodium, , cicleSonide, cicletanine, CiclopiroX, Ciclopro , darlucin A, , darsidomine, Daunoru fen, , Cidofovir, Hydrochloride, bicin Hydrochloride, Dazadrol Maleate, Dazepinil Hydro Cifenline, Ciglitazone, Hydrochloride, , chloride, Dazmegrel, Fumarate, Dazoxiben Cilastatin Sodium, CilaZapril, , Hydrochloride, Debrisoquin Sulfate, Decitabine, defer MeSylate, cilobradine, Cillofungin, ciloStaZol, , iprone, deflazacort, Dehydrocholic Acid, dehydrodidemnin Cimetidine, cimetropium bromide, Cinalukast, B, , delapril, Delapril Hydrochlo Hydrochloride, Cinepazet Maleate, Cinflumide, , ride, Delavirdine MeSylate, deleguamine, delfaprazine, Del , , , , Cino madinone Acetate, delmopinol, delphinidin, Demecarium Xacin, Cinperene, Cinromide, CintaZone, Cintriamide, Ciot Bromide, Demeclocycline, Demecycline, , eronel, Cipamfylline, Ciprefadol Succinate, Ciprocinonide, Denofungin, deoxypyridinoline, Depakote, deprodone, Ciprofibrate, Ciprofloxacin, ciprostene, Ciramadol, Cirole Deprostil, depSidomycin, , dermatan Sulfate, mycin, , cisatracurium besilate, Cisconazole, Cis Desciclovir, Descinolone Acetonide, , platin, cis-porphyrin, cistinexine, citalopram, Citenamide, Hydrochloride, desirudin, Deslanoside, citicoline, citreamicin alpha, cladribine, Clamoxyquin deslorelin, desmopressin, , DeSonide, DeS Hydrochloride, , clausenamide, Clavulanate Oximetasone, desoxoamiodarone, DeSoxycorticosterone Potassium, , Clazolimine, , , Acetate, detajmium bit artrate, Hydrochloride, Maleate, Clidinium Bromide, clinafloxacin, Detirelix Acetate, , Dexamethasone, Dexami Clindamycin, Clioquinol, Clioxanide, Cliprofen, , Sole, Maleate, Clobetasol Propionate, Clobetasone Butyrate, Clocortolone Maleate, Dexclamol Hydrochloride, Dexetimide, Dexfen Acetate, Clodanolene, Clodazon Hydrochloride, clodronic fluramine Hydrochloride, dexifosfamide, Deximafen, Dexi acid, Clofazimine, Clofibrate, Clofilium Phosphate, Cloge vacaine, dexketoprofen, dexloxiglumide, DeXmedetomi Stone Acetate, Clomacran Phosphate, dine, DeXormaplatin, Dexoxadrol Hydrochloride, Acetate, Clometherone, , clomifene ana Dexpanthenol, Dexpemedolac, Dexpropranolol Hydrochlo logues, , Clomiphene, Hydro ride, DeXraZOxane, deXSotalol, dextrin 2-Sulphate, Dextro chloride, , Clonidine, Clonitrate, Clonixeril, amphetamine, , Dextrorphan Hydrochlo Clonixin, Clopamide, , Cloperidone Hydro ride, Dextrothyroxine Sodium, deXVerapamil, DeZaguanine, chloride, clopidogrel, , Clopipazan MeSylate, dezinamide, deZOcine, Hydrochloride, Clopirac, Cloprednol, Cloprostenol Sodium, Diamocaine Cyclamate, Diapamide, Diatrizoate Meglu Dipotassium, Clorethate, Clorexolone, Cloroperone Hydro mine, Diatrizoic Acid, Diaveridine, , Diaziquone, chloride, Clorprenaline Hydrochloride, Clorsulon, Clorter , Hydrochloride, Dibenzothiophene, mine Hydrochloride, CloSantel, Closiramine Aceturate, Dibucaine, Dichliorvos, , Dichlorphe Clothiapine, Clothixamide Maleate CloticaSone Propionate, namide, , Diclofenac Sodium, Dicloxacillin, dic Clotrimazole, Cloxacillin BenZathine, Cloxyquin, CloZap ranin, Dicumarol, Dicyclomine Hydrochloride, Didanosine, ine, , Coccidioidin, Codeine, Codoxime, Colchicine, didemnin B, didox, Dienestrol, , Diethylcarbam colestimide, Colestipol Hydrochloride, Colestolone, Col azine Citrate, diethylhomospermine, diethylnorspermine, forsin, Colfosceril Palmitate, Colistimethate Sodium, Colis Diethylpropion Hydrochloride, Diethylstilbestrol, Difenox tin Sulfate, collismycin A, collismycin B, Mesylate, imide Hydrochloride, Difenoxin, Diflorasone Diacetate, combretastatin A4, combretastatin analogue, complestatin, Difloxacin Hydrochloride, Difluanine Hydrochloride, Diflu US 2006/OO18933 A1 Jan. 26, 2006

cortolone, Diflumidone Sodium, Diflunisal, Difluprednate, Hydrochloride, Eugenol, Euprocin Hydrochloride, eveni Diftalone, Digitalis, , , Dihexyverine nomicin, Exametazime, examorelin, Hydrochlo Hydrochloride, , dihydro-5-azacytidine, Dihy ride, , fadrozole, faerieflungin, Famciclovir, drocodeine Bitartrate, Mesylate, Dihy Famotidine, Fampridine, , Fantridone Hydro droestosterone, Dihydrostreptomycin Sulfate, Dihydrotach chloride, faropenem, fasidotril, , faZarabine, fedot ysterol, dihydrotaxol, 9-, Dilantin, Dilevalol Hydrochloride, Ozine, felbamate, Felbinac, , Fely pressin, Fenala Hydrochloride, Dimefadane, Dimefline Hydro mide, Fenamole, Fenbendazole, Fenbufen, Fencibutirol, chloride, , Dimercaprol, Dimethadione, Fenclofenac, , Fenclorac, Fendosal, FeneStrel, Dimethindene Maleate, , dimethyl prostag Hydrochloride, Hydrochloride, landin A1, Dimethyl Sulfoxide, dimethylhomospermine, Fengabine, Fenimide, , Hydrochlo dimiracetam, Dimoxamine Hydrochloride, Dinoprost, Dino ride, , Fenobam, Fenoctimine Sulfate, fenofi prostone, Dioxadrol Hydrochloride, dioxamycin, Diphenhy brate, , Fenoprofen, , Fenpipalone, dramine Citrate, Diphenidol, Diphenoxylate Hydrochloride, Fenprinast Hydrochloride, Fenprostalene, Fenguizone, fen diphenyl spiromustine, Dipivefin Hydrochloride, Dipivefrin, retinide, , Citrate, Fentiazac, Fenticlor, dipliencyprone, , dipropylnorspermine, Dipy fenticonazole, Fenyripol Hydrochloride, fepradinol, ferpifo ridamole, Dipyrithione, Dipyrone, dirithromycin, discoder Sate Sodium, ferristene, ferriXan, Ferrous Sulfate, Dried, mollide, Disobutamide, Disofenin, , Disoxaril, Ferumoxides, ferumoxsil, Fetoxylate Hydrochloride, fex disulfiram, Ditekiren, Divalproex Sodium, ofenadine, Fumarate, Fiacitabine, Fialuridine, Maleate, , docarpamine, Docebenone, Doc Fibrinogen 1125, filgrastim, Filipin, finasteride, Flavodilol etaxel, Doconazole, docOSanol, dolfetilide, , Ebas Maleate, flavopiridol, Flavoxate Hydrochloride, Flazalone, tine, ebiratide, , ebSelen, ecabapide, ecabet, eca , flerobuterol, Fleroxacin, , dotril, ecdisteron, echicetin, echistatin, Echothiophate Sulfate, , flezelastine, flobufen, Floctafenine, flo Iodide, Eclanamine Maleate, EclaZolast, ecomustine, Econa moxef, Flordipine, florfenicol, florifenine, flosatidil, Flose Zole, ecteinascidin 722, edaravone, Edatrexate, edelfosine, quinan, Floxacillin, Floxuridine, fluiasterone, Fluazacort, Edifolone Acetate, edobacomab, Edoxudine, edrecolomab, Flubanilate Hydrochloride, Flubendazole, , Flu Edrophonium Chloride, edroxyprogesteone Acetate, efegat cloronide, Fluconazole, Flucytosine, Fludalanine, Fludara ran, eflornithine, , egualcen, Elantrine, eleatonin, bine Phosphate, Fludazonium Chloride, Fludeoxyglucose F elemene, , elgodipine, eliprodil, Elsamitrucin, elte 18, , Acetate, , nae, Elucaine, emalkalim, , Emetine Hydrochlo Flufenisal, , flumecinol, Flumequine, Flumeri ride, emiglitate, Emilium Tosylate, emitefur, emoctakin, done, Flumethasone, Flumetramide, , Flumi Enadoline Hydrochloride, enalapril, Enalaprilat, Enalkiren, norex, Flumizole, Flumoxonide, , Flunidazole, enaZadrem, Encyprate, Endralazine MeSylate, EndrySone, Flunisolide, , Flunixin, fluocalcitriol, Fluoci , englitaZone, Enilconazole, Enisoprost, Enlimo nolone Acetonide, Fluocinonide, Fluocortin Butyl, Fluocor mab, Enloplatin, Enofelast, Enolicam Sodium, Enoxacin, tolone, Fluorescein, fluorodaunorunicin hydrochloride, enoxacin, enoxaparin Sodium, Enoxaparin Sodium, Enoxi Fluorodopa F 18, , Fluorouracil, Flu mone, Enpiroline Phosphate, Enprofylline, Enpromate, enta otracen Hydrochloride, , , flup capone, enterostatin, Enviradene, EnviroXime, , aroXan, Fluperamide, Fluperolone Acetate, Epicillin, Epimestrol, Epinephrine, Epinephryl Borate, Decanoate, , Fluprednisolone, FluproduaZone, Flu Epipropidine, Epirizole, epirubicin, Epitetracycline Hydro prostenol Sodium, FluguaZone, Fluradoline Hydrochloride, chloride, Epithiazide, Epoetin Alfa, Epoetin Beta, EpoproS Flurandrenolide, Hydrochloride, Flurbiprofen, tenol, Epoprostenol Sodium, epoxymeXrenone, epristeride, Fluretofen, flurithromycin, Flurocitabine, Flurofamide, EproSartan, eptastigmine, equilenin, Equilin, Erbulozole, Flurogestone Acetate, , , Fluspiperone, erdosteine, MeSylates, Ergonovine Maleate, , Fluticasone Propionate, flutrimazole, Flutro Tartrate, , ErSofermin, erythritol, line, fluvastatin, Fluvastatin Sodium, , FluZina Erythrityl Tetranitrate, Erythromycin, Hydrochlo mide, Folic Acid, Follicle regulatory protein, Folliculostatin, ride, Esorubicin Hydrochloride, Esprocquin Hydrochloride, Fomepizole, Fonazine MeSylate, forasartan, forfenimex, for , Estradiol, , estramustine analogue, fenirmex, , Formocortal, , Fosarilate, EstraZinol Hydrobromide, Estriol, Estrofurate, estrogen ago , Foscarnet Sodium, fosfomycin, Fosfonet nists, estrogen antagonists, Estrogens, Conjugated, Estro Sodium, foSinopril, Fosinoprilat, , Fosquidone, gens, Esterified, Estrone, Estropipate, eSuprone, , fostriecin, fotemustine, Fuchsin, Basic, Fumoxicil Hydrochloride, Etanidazole, etanterol, Etarotene, lin, Fungimycin, Furaprofen, Furazolidone, Furazolium Hydrochloride, , ethacizin, Ethacrynate Sodium, Chloride, Furegrelate Sodium, Furobufen, Furodazole, Ethacrynic Acid, Ethambutol Hydrochloride, Ethamivan, , Fusidate Sodium, Fusidic Acid, gabapentin, Ethanolamine Oleate, Ethehlorvynol, Ether, Ethinyl estra Gadobenate Dimeglumine, gadobenic acid, gadobutrol, diol, Ethiodized Oil, Ethionamide, Ethonam Nitrate, Etho Gadodiamide, gadolinium teXaphyrin, Gadopentetate propazine Hydrochloride, EthosuXimide, , Ethoxa Dimeglumine, gadoteric acid, Gadoteridol, Gadoverseta Zene Hydrochloride, Ethybenztropine, Ethyl Chloride, Ethyl mide, galantamine, galdansetron, Galdansetron Hydrochlo Dibunate, , Ethyndiol, , Ethynodiol ride, Gallamine Triethiodide, gallium nitrate, , Diacetate, Etibendazole, , Etidronate Disodium, galocitabine, Gamfexine, gamolenic acid, Ganciclovir, Etidronic Acid, Etifenin, Etintidine Hydrochloride, eti ganirelix, gelatinase inhibitors, Gemcadiol, Gemcitabine, Zolam, Etodolac, Etofenamate, Etoformin Hydrochloride, Gemeprost, Gemfibrozil, Gentamicin Sulfate, Gentian Vio , , Hydrochloride, Eto let, , , , GeStonorone poside, Etoprine, Etoxadrol Hydrochloride, EtoZolin, etra Caproate, , Hydrochloride, giriso bamine, Etretinate, Etryptamine Acetate, Eucatropine pam, glaspimod, glaucocalyxin A, , Gliamilide, US 2006/OO18933 A1 Jan. 26, 2006

Glibornuride, Glicetanile Sodium, Gliflumide, , Iotyrosine 1 131, IoverSol, Ioxagiate Sodium, Ioxaglate , Gloximonam, Glucagon, glutapyrone, glutathione Meglumine, Ioxaglic Acid, ioxilan, Ioxotrizoic Acid, ipazil inhibitors, , Glyburide, glycopine, glycopril, ide, ipenoxazone, ipidacrine, Ipodate Calcium, ipomeanol, Glycopyrrolate, Glyhexamide, Glymidine Sodium, Glyoc 4-, pratropium Bromide, ipriflavone, , Iprofenin, tamide, Glyparamide, Gold Au 198, Gonadoctrinins, Gona Ipronidazole, proplatin, Iproxamine Hydrochloride, ipsa dorelin, Gonadotropins, Goserelin, Gramicidin, , pirone, irbesartan, irinotecan, irloxacin, iroplact, irSoglad grepafloxacin, Griseofulvin, Guaiapate, Guaithylline, Gua ine, Irtemazole, isalsteine, Isamoxole, isbogrel, Isepamicin, nabenz, , Acetate, Sulfate, Guancy isobengaZole, Isobutamben, , ISOconazole, dine, Monosulfate, Hydrochlo Isoetharine, isofloxythepin, Isoflupredone Acetate, Isoflu ride, Guanisoquin Sulfate, Sulfate, Guanoctine rane, Isoflurophate, isohomohalicondrin B, Isoleucine, Iso Hydrochloride, , Sulfate, Guanoxy mazole Hydrochloride, Isomylamine Hydrochloride, Iso fen Sulfate, Gusperimus Trihydrochloride, , Hal niazid, Isopropamide Iodide, , isopropyl cinonide, halichondrin B, Halobetasol Propionate, halofan unoprostone, Isoproterenol Hydrochloride, ISOSorbide, ISOS trine, Halofantrine Hydrochloride, Halofenate, orbide Mononitrate, Isotiquimide, Isotretinoin, ISOXepac, Halofuginone Hydrobromide, halomon, Halopemide, Halo ISOXicam, Hydrochloride, , itameline, peridol, halopredone, , Haloprogin, Hal itasetron, ItaZigrel, , Itraconazole, , jas othane, Halquinols, Hamycin, Han memopausal gonadotro plakinolide, Josamycin, kahalalide F, Kalafungin, Kanamy pins, hatomamicin, hatomarubigin A, hatomarubigin B, cin Sulfate, Hydrochloride, , Ketazo hatomarubigin C, hatomarubigin D, Heparin Sodium, hep cine, , Kethoxal, Ketipramine Fumarate, Sulfam, heregulin, Hetacillin, Heteronium Bromide, , Ketoprofen, Ketorfanol, ketorolac, Hexachlorophene:Hydrogen Peroxide, Hexafluorenium Fumarate, Kitasamycin, Hydrochloride, Lacid Bromide, hexamethylene bisacetamide, Hexedine, Hex ipine, , lactitol, lactivicin, laennec, , obendine, Sulfate, Hexylresorcinol, Hista lamellarin-N triacetate, lamifiban, Lamivudine, Lamot mine Phosphate, , Histoplasmin, Histrelin, Homa rigine, lanoconazole, Lanoxin, lanperisone, lanreotide, Lan tropine Hydrobromide, Hoquizil Hydrochloride, Human Soprazole, latanoprost, lateritin, laurocapram, Lauryl Iso chorionic gonadotropin, Hycanthone, Hydralazine Hydro quinolinium Bromide, Succinate, , chloride, Hydralazine Polistirex, Hydrochlorothiazide, Lecimibide, leinamycin, lemildipine, leminoprazole, lener Hydrocodone Bitartrate, , Hydroflumethiaz cept, Leniquinsin, lenograstim, , lentinan Sulfate, ide, Hydromorphone Hydrochloride, Hydroxyamphetamine leptin, leptolstatin, , , , Hydrobromide, Hydroxychloroquine Sulfate, Hydroxyphe Letimide Hydrochloride, letraZuril, letrozole, Leucine, leu namate, Hydroxyprogesterone Caproate, Hydroxyurca, comyzin, Leuprolide Acetate, leuprolide--estrogen-proges Hydroxyzine Hydrochloride, Hymecromone, Hyoscyamine, terone, leuprorelin, Levamfetamine Succinate, levamisole, hypericin, Ibafloxacin, ibandronic acid, , Ibopam Levdobutamine Lactobionate, Leveromakalim, levetirac ine, ibudilast, Ibufenac, , Fumarate, Icati etam, Levey closerine, , , levobupi bant Acetate, Ichthammol, Icotidine, idarubicin, idoxifene, vacaine, , levocarnitine, Levodopa, levodro Idoxuridine, idramantone, Iemefloxacin, IeSopitron, propizine, levofloxacin, Levofuraltadone, Levoleucovorin Ifetroban, Ifosfamide, Ilepeimide, illimaquinone, ilmofoS Calcium, Levomethadyl Acetate, Levomethadyl Acetate ine, ilomastat, Ilonidap, illoperidone, iloprost, Imafen Hydro Hydrochloride, , Levonantradol Hydrochlo chloride, ImaZodan Hydrochloride, imidapril, , ride, Levonordefrin, Levonorgestrel, Levopropoxyphene imidazoacridones, Imidecyl Iodine, Imidocarb Hydrochlo NapSylate, Levopropylcillin Potassium, leVormeloxifene, ride, Imidoline Hydrochloride, Imidurea, Hydro Levorphanol Tartrate, levosimendan, , chloride, Imipenem, Hydrochloride, imiqui Levothyroxine Sodium, Levoxadrol Hydrochloride, Lexi mod, immunostimulant peptides, pafant, Lexithromycin, liarozole, Libenzapril, Lidamidine Hydrochloride, Indacrinone, Indapamide, Indecainide Hydrochloride, , Lidofenin, , Lifariz Hydrochloride, Hydrochloride, Indigotindisul ine, Lifibrate, Lifibrol, Linarotene, Lincomycin, linear fonate Sodium, indinavir, Indocyanine Green, Indolapril polyamine analogue, Linogliride, , linotroban, Hydrochloride, Indolidan, indometacin, Indomethacin linsidomine, lintitript, lintopride, Liothyronine I 125, liothy Sodium, Indoprofen, , Hydrochloride, ronine Sodium, Liotrix, lirexapride, lisinopril, lisSoclinamide Indoxole, Indriline Hydrochloride, , inogatran, 7, Lixazinone Sulfate, lobaplatin, Lobenzarit Sodium, Lobu inolimomab, InoSitol Niacinate, Insulin, interferons, inter cavir, Lodelaben, lodoxamide, Lofemizole Hydrochloride, leukins, Intrazole, Hydrochloride, iobenguane, Lofentanil Oxalate, Hydrochloride, Iobenzamic Acid, iobitridol, Iocarmate Meglumine, Iocar Hydrochloride, lombricine, Lomefloxacin, , mic Acid, Iocetamic Acid, Iodamide, Iodine, Iodipamide Lometraline Hydrochloride, lometrexol, Lomofungin, Meglumine, Iodixanol, iodoamiloride, Iodoantipyrine I 131, Lomoxicam, Lomustine, Lonapalene, lonazolac, Iodocholesterol I 131, iododoxorubicin, Iodohippurate , Hydrochloride, loracarbef, Sodium I 131, Iodopyracet I 125, Iodoquinol, Iodoxamate Hydrochloride, , Lorazepam, Lorbam Meglumine, Iodoxamie Acid, Ioglicic Acid, ate, Lorcainide Hydrochloride, , Loreinadol, lor Hydrochloride I 123, iofratol, Ioglucol, Ioglucomide, Iogly glumide, , Lornoxicam, lornoxicam, Lorta camic Acid, Iogulamide, Iohexol, iomeprol, Iomethin I 125, lamine, LorZafone, losartan, losigamone, loSOXantrone, Iopamidol, Iopanoic Acid, iopentol, Iophendylate, Ioproce LOSulazine Hydrochloride, loteprednol, lovastatin, loviride, mic Acid, iopromide, Iopronic Acid, Iopydol, Iopy done, , Loxoribine, lubeluzole, Lucanthone Hydrochlo iopyrol, Iosefamic Acid, IoSeric Acid, IoSulamide Meglu ride, Lufironil, Lurosetron MeSylate, lurtotecan, luteinizing mine, IoSumetic Acid, IotaSul, Iotetric Acid, Iothalamate hormone, lutetium, Lutrelin Acetate, luZindole, Lyapolate Sodium, Iothalamic Acid, iotriside, Iotrolan, IotroXic Acid, Sodium, Lycetamine, lydicamycin, Lydimycin, , US 2006/OO18933 A1 Jan. 26, 2006

Lypressin, Lysine, lySofylline, lysostaphin, lytic peptides, Mitindomide, Mitocarcin, Mitocromin, Mitogillin, mitogua Maduramicin, Mafenide, magainin 2 amide, Magnesium Zone, mitolactol, Mitomalcin, Mitomycin, mitonafide, Mito Salicylate, Magnesium Sulfate, , maitansine, Male Sper, Mitotane, mitoxantrone, mivacurium chloride, mivaZ thamer, mallotochromene, mallotojaponin, Malotilate, erol, mixanpril, Mixidine, , mizoribine, malotilate, mangafodipir, , maniwamycin A, , , Modaline Sulfate, Modecainide, Mannitol, mannostatin A, manumycin E, manumycin F, moexipril, mofarotene, Mofegiline Hydrochloride, mof mapinastine, , marimastat, Martek 8708, Martek eZolac, molgramoStim, MolinaZone, Hydrochlo 92211, Masoprocol, maspin, massetolide, matrilysin inhibi ride, Molsidomine, , Maleate, Mon tors, Maytansine, Succiniate, , ensin, Monoctanoin, Montelukast Sodium, montirelin, Mebendazole, Mebeverine Hydrochloride, Mebrofenin, mopidamol, , Morantel Tartrate, Moricizine, , Hydrochloride, Mechlore Morniflumate, Sulfate, Morrhuate Sodium, thamine Hydrochloride, Meclocycline, Meclofenamate , , motilide, Motretinide, Moxalac Sodium, , Meclorisone Dibutyrate, tam Disodium, Moxazocine, moxiraprine, Moxinidazole, Hydrochloride, Medorinone, , , Mumps Skin Test Antigen, mustard anticancer , , Medrysone, Meelizine agent, Muzolimine, mycaperoxide B, Mycophenolic Acid, Hydrochloride, , Mefenidil, myriaporone, Nabazenil, , Nabitan Hydrochloride, Hydrochloride, , Hydrochloride, Naboctate Hydrochloride, Nabumetone, N-acetyldinaline, Mefruside, Megalomicin Potassium Phosphate, Nadide, nadifloxacin, , nadroparin calcium, nafadot Acetate, Meglumine, Meglutol, Acetate, Meli ride, nafamoStat, nafarelin, Nafcillin Sodium, Nafenopin, tracen Hydrochloride, Melphalan, Memotine Hydrochlo Nafimidone Hydrochloride, Naflocort, Nafomine Malate, ride, Menabitan Hydrochloride, Menoctone, menogaril, Nafoxidine Hydrochloride, Nafronyl Oxalate, Naftifine Menotropins, Meobentine Sulfate, Mepartricin, Mepen Hydrochloride, , naglivan, nagreStip, Nalbuphine Zolate Bromide, Meperidine Hydrochloride, Hydrochloride, Nalidixate Sodium, Nalidixic Acid, Sulfate, , Mephobarbital, Hydro nalmefene, NalmeXOne Hydrochloride, -pentazo chloride, , Meptazinol Hydrochloride, Mequi cine, , NamoXyrate, Phenpropionate, , Meralein Sodium, merbarone, Mercaptopurine, Mer Nantradol Hydrochloride, Napacitadine Hydrochloride, cufenol Chloride, Mercury, Ammoniated, Merisoprol Hg napadisilate, Napamezole Hydrochloride, napavin, Nap 197, Meropenem, Mesalamine, Meseclazone, , hazoline Hydrochloride, naphterpin, Naproxen, NaproXol, , Mestranol, Mesuprine Hydrochloride, Metalol napsagatran, Hydrochloride, Narasin, , Hydrochloride, Metaproterenol Polistirex, nartograstim, nasaruplase, Natamycin, nateplase, Nax Bitartrate, Metaxalone, Meteneprost, meterelin, Metformin, agolide Hydrochloride, , Nebramycin, nedaplatin, Methacholine Chloride, Methacycline, Methadone Hydro Nedocromil, Hydrochloride, Neflumozide chloride, Methadyl Acetate, Methalthiazide, Methamphet Hydrochloride, Hydrochloride, NeleZaprine Male amine Hydrochloride, , Methazolamide, ate, Nemazoline Hydrochloride, nemorubicin, Neomycin , Methenamine, Methenolone Acetate, Meth Palmitate, Neostigmine Bromide, neridronic acid, Netilmi etoin, Methicillin Sodium, Methimazole, methioninase, cin Sulfate, neutral endopeptidase, Neutramycin, Nevirap Methionine, Methisazone, Methixene Hydrochloride, ine, Nexeridine Hydrochloride, Niacin, Nibroxane, Nicar , Sodium, Methopholine, dipine Hydrochloride, , Niclosamide, Methotrexate, Methotrimeprazine, methoxatone, Methoxy , , , Nifirmerone, flurane, Methsuximide, Methyclothiazide, Methyl Palmox Nifluridide, Nifuradene, Nifuraldezone, Nifuratel, Nifura irate, Methylatropine Nitrate, Methylbenzethonium Chlo trone, Nifurdazil, Nifurimide, Nifurpirinol, Nifurcquinazol, ride, , Methyldopate Hydrochloride, Methylene Nifurthiazole, , , Nimazone, Nimo Blue, Methylergonovine Maleate, methylhistamine, R-al dipine, , niravoline, Niridazole, nisamycin, Nis pha, methylinosine monophosphate, Methylphenidate buterol Mesylate, nisin, , , Nisoxet Hydrochloride, Methylprednisolone, , ine, Acetate, NitarSone, nitaZOXanide, nitecapone, Methynodiol Diacelate, , Methysergide Male Nitrafudam Hydrochloride, Nitralamine Hydrochloride, Nit ate, , , Metioprim, metipamide, ramisole Hydrochloride, , , Nitrocy , Metizoline Hydrochloride, Metkephamid cline, Nitrodan, Nitrofurantoin, Nitrofurazone, Nitroglyc Acetate, , Metocurine Iodide, , erin, Nitromersol, Nitromide, Nitromifene Citrate, Nitrous Metolazone, , Metoprine, Metoprolol, Meto Oxide, nitroxide antioxidant, nitrullyn, Nivazol, Nivine quizine, metrifonate, Metrizamide, Metrizoate Sodium, done Sodium, , Noberastine, Nocodazole, Metronidazole, Meturedepa, Metyrapone, Metyrosine, Nogalamycin, Nolinium Bromide, Maleate, Hydrochloride, , Noracymethadol Hydrochloride, Norbolethone, Norepi Mezlocillin, mfonelic Acid, Hydrochloride, nephrine Bitaritrate, Norethindrone, Norethynodrel, Nor , Mibefradil Dihydrochloridc, , mich floxacin, Norflurane, , , Norg ellamine B, Miconazole, microcolin A, , Mida estrel, Nortriptyline Hydrochloride, NoScapine, Novobiocin Zolam Hydrochloride, , , Mifobate, Sodium, N-Substituted benzaimides, NufenoXole, miglitol, millacemide, milameline, mildronate, Milenperone, Nylestriol, Nystatin, O6-benzylguanine, Obidoxime Chlo Milipertine, , Milrinone, miltefosine, Mimbane ride, , Ocfentanil Hydrochloride, , Hydrochloride, , , Minocromil, Octanoic Acid, Octazamide, Octenidine Hydrochloride, Minocycline, , Mioflazine Hydrochloride, mioka , Octreotide, Phosphate, Ofloxacin, mycin, mipragoside, mirfentanil, mirimoStim, Mirincamy Ofornine, okicenone, , oligonucleotides, olopata cin Hydrochloride, Mirisetron Maleate, , mis dine, olprinone, olSalazine, Olsalazine Sodium, Olvanil, matched double stranded RNA, Misonidazole, Misoprostol, omeprazole, , , Ontazolast, Oocyte US 2006/OO18933 A1 Jan. 26, 2006 maturation inhibitor, Hydrochloride, oracin, , PipaZethate, pipecuronium bromide, Piperac Orconazole Nitrate, Orgotein, Orlislat, Ormaplatin, Orme etazine, Piperacillin Sodium, Piperamide Maleate, Pipera toprim, Ornidazole, Orpanoxin, Citrate, zine, Pipobroman, Piposulfan, Palmitate, , otenZepad, Oxacillin Sodium, OXagrelate, Oxali Pipoxolan Hydrochloride, Piprozolin, Hydro platin, OXamarin Hydrochloride, oxamisole, Oxamniquine, chloride, Piquizil Hydrochloride, Piracetam, , Oxantel Pamoate, Hydrochlo Hydrochloride, pirarubicin, Pirazmonam Sodium, Pirazolac, ride, Oxaprozin, OXarbazole, , oxaunomycin, Pirbenicillin Sodium, Acetate, , , , , Oxethazaine, Hydrochloride, , Pirfenidone, Piridi Fumarate, Oxfendazole, Oxfenicine, Oxibenda cillin Sodium, Piridironate Sodium, Piriprost, piritrexim, Zole, oxiconazole, , Oxidronic Acid, OXifungin Pirlimycin Hydrochloride, , pirmagrel, Pirmenol Hydrochloride, Oxilorphan, Oximonam, Oximonam Hydrochloride, Pirnabine, Piroctone, Pirodavir, pirodomast, Sodium, OXiperomide, , OXiramide, Oxisuran, Pirogliride Tartrate, , Pirolazamide, Piroxantrone Oximetidine Hydrochloride, , Phen Hydrochloride, Piroxicam, Piroximone, Pirprofen, Pirquino propionate, , Hydrochloride, Oxt Zol, Pirsidomine, , Pituitary, Posterior, Pivampi riphylline, oxybutynin Chloride, Oxychlorosene, Oxyc cillin Hydrochloride, Pivopril, Pizotyline, placetin A, plati odone, Hydrochloride, , num compounds, platinum-triamine complex, Plicamycin, Oxymorphone Hydrochloride, Oxypertine, Oxyphenbuta , Pobilukast Edamine, Podofilox, Poisonoak Zone, Oxypurinol, Oxytetracycline, Oxytocin, OZagrel, OZO Extract, Poldine Methylsulfate, Poliglusam, Polignate linone, Paclitaxel, palauamine, Paldimycin, palinavir, palmi Sodium, Polymyxin B Sulfate, Polythiazide, Ponalrestat, toylrhizoxin, Palmoxirate Sodium, pamaqueside, Porfimer Sodium, Porfiromycin, Potassium Chloride, Potas Sulfate, pamicogrel, Pamidronate Disodium, pamidronic sium Iodide, Potassium Permanganate, PoVidone-Iodine, acid, , , panaxytriol, Pancopride, , Pralidoxime Chloride, Pramiracetam Hydrochlo Pancuronium Bromide, panipenem, pannorin, panomifene, ride, Pramoxine Hydrochloride, Pranolium Chloride, Prava pantethine, pantoprazole, Papaverine Hydrochloride, para doline Maleate, Pravastatin (Pravachol), , Pra bactin, Parachlorophenol, , Paramethasone Zosin, Hydrochloride, , , Acetate, Paranyline Hydrochloride, Parapenzolate Bromide, , Prednisolone, , Prednival, Preg Pararosaniline Pamoate, Parbendazole, Parconazole Hydro menolone Succiniate, Hydrochloride, chloride, Paregoric, Pareptide Sulfate, Hydrochlo Hydrochloride, Prifelone, Hydrochloride, ride, parnaparin sodium, Paromomycin Sulfate, Paroxetine, Prilosec, Primaquine Phosphate, , , parthenolide, Partricin, Paulomycin, paZelliptine, PaZina Prinivil, Prinomide Tromethamine, Prinoxodan, Prizidilol clone, PaZOxide, paZufloxacin, pefloxacin, pegaspargase, Hydrochloride, Hydrochloride, Probenecid, Pro Pegorgotein, Hydrochloride, peldesine, Peliomy bicromil Calcium, Probucol, Hydrochloride, cin, Pelretin, Pelrinone Hydrochloride, Pemedolac, Pemerid Hydrochloride, Procarbazine Hydrochloride, Pro Nitrate, pemirolast, , Penamecillin, Sul caterol Hydrochloride, , Procinonide, Pro fate, Penciclovir, , Penicillin G BenZathine, Peni clonol, Procyclidine Hydrochloride, Prodilidine Hydrochlo cillin G Potassium, Penicillin G Procaine, Penicillin G ride, Prodolic Acid, Profadol Hydrochloride, Progabide, Sodium, Penicillin V, Penicillin V BenZathine, Penicillin V Progesterone, Proglumide, Proinsulin Human, Proline, Pro Hydrabamine, Penicillin V Potassium, , Pen lintane Hydrochloride, Hydrochloride, Promet taerythritol Tetranitrate, pentafuside, pentamidine, pentam hazine Hydrochloride, Hydrochloride, orphone, Pentamustine, Pentapiperium Methylsulfate, Pen propagermanium, , Propantheline Bromide, Pro tazocine, Pentetic Acid, Pentiapine Maleate, pentigetide, paracaine Hydrochloride, Propatyl Nitrate, propentofylline, Pentisomicin, Pentizidone Sodium, , Pento Propenzolate Hydrochloride, Propikacin, , mone, Pentopril, pentosan, pentostatin, , Pen Propionic Acid, propionylcarnitine, L-, propiram, propiram-- trinitrol, pentrozole, Peplomycin Sulfate, Pepstatin, perflu paracetamol, propiverine, , Hydro bron, perfofamide, Perfosfamide, , chloride, Propoxyphene Hydrochloride, Hydro Maleate, perillyl alcohol, Perindopril, perindoprilat, Perlap chloride, Propulsid, propyl bis-acridone, , ine, Permethrin, , , , Propyliodone, Propylthiouracil, ProquaZone, Prorenoate phenaridine, phenazinomycin, Phenazopyridine Hydrochlo Potassium, Proroxan Hydrochloride, Proscillaridin, Prostal ride, Phenbutazone Sodium Glycerate, Phencarbamide, ene, prostratin, Protamine Sulfate, protegrin, Protirelin, pro Hydrochloride, Tartrate, toSufloxacin, Hydrochloride, Proxazole, ProX Sulfate, Hydrochloride, Phe azole Citrate, ProXicromil, Proxorphan Tartrate, nobarbital, Hydrochloride, Phenprocou prulifloxacin, Hydrochloride, Puromycin, mon, phenserine, phensuccinal, , Phenter purpurins, Pyrabrom, Pyrantel Pamoate, Pyrazinamide, mine, Hydrochloride, mesilate, Pyrazofurin, pyrazoloacridine, PyridoStigmine Bromide, Phentoxifylline, Phenyl Aminosalicylate, phenylacetate, Pyrilamine Maleate, Pyrimethamine, Pyrinoline, Pyrithione , phenylalanylketoconazole, PhenylbutaZone, Sodium, Pyrithione , Hydrochloride, Hydrochloride, Pyroxamine Maleate, Pyrrocaine, Pyrroliphene Hydrochlo Hydrochloride, Phenylpropanolamine Polistirex, Phenyra ride, Pyrrolnitrin, Pyrvinium Pamoate, Quadazocine Mesy midol Hydrochloride, Phenytoin, phosphatase inhibitors, late, , Quazinone, QuaZodine, QuaZolast, quetiap PhySoStigmine, picenadol, picibanil, Picotrin Diolamine, ine, quiflapon, , Quinaldine Blue, quinapril, picroliv, picumeterol, pidotimod, Pifarnine, Pilocarpine, pil Quinaprilat, Hydrochloride, , Quinc Sicainide, pimagedine, Pimetine Hydrochloride, pimilprost, tolate, Quindecamine Acetate, Quindonium Bromide, Pimobendan, , , Pinadoline, , pin Hydrochloride, Quinestrol, Quinfamide, nenol, pinocebrin, Hydrochloride, pioglitaZone, Acetate, , Gluconate, US 2006/OO18933 A1 Jan. 26, 2006

Quinielorane Hydrochloride, Quinine Sulfate, Hydrochloride, Spiromustine, , Spiroplatin, Hydrochloride, Quinterenol Sulfate, Quinuclium Bromide, SpiroXasone, Splenopentin, Spongistatin 1, Sprodiamide, Quinupristin, Quilpazine Maleate, Rabeprazole Sodium, squalamine, Stallimycin Hydrochloride, Stannous Pyro Racephenicol, Racepinephrine, raf antagonists, Rafoxanide, phosphate, Stannous Sulfur Colloid, , Statolon, Ralitoline, raloxifene, raltitrexed, ramatroban, Ramipril, StauroSporine, Stavudine, Steffimycin, Acetate, Ramoplanin, , ranelic acid, Ranimycin, Raniti Stepronin, Stilbazium Iodide, Stilonium Iodide, Stipiamide, dine, , Rauwolfia Serpentina, recainam, Recainam , Stobadine, Streptomycin Sulfate, StreptonicOZid, Hydrochloride, , regaVirumab, RegramoStim, Streptonigrin, Streptozocin, Stromelysin inhibitors, Stron Relaxin, Relomycin, Hydrochloride, Remifen tium Chloride Sr 89, succibun, Succimer, Succinylcholine tanil Hydrochloride, Remiprostol, , Repirinast, Chloride, Sucralfate, Sucrosofate Potassium, Sudoxicam, Repromicin, Hydrochloride, , resin , , , Sulbactam Pivoxil, Sul feratoxin, Resorcinol, retelliptine demethylated, reticulon, conazole Nitrate, Sulfabenz, Sulfabenzamide, Sulfaceta reviparin Sodium, revizinone, rhenium Re 186 etidronate, mide, Sulfacytine, Sulfadiazine, Sulfadoxine, Sulfalene, rhizoxin, Ribaminol, Ribavirin, Riboprine, ribozymes, Sulfamerazine, Sulfameter, Sulfamethazine, Sulfamethizole, , Ridogrel, Rifabutin, Rifametane, Rifamexil, Sulfamethoxazole, Sulfamonomethoxine, Sulfamoxole, Sul Rifamide, Rifampin, Rifapentine, Rifaximin, RII retina fanilate Zinc, Sulfanitran, SulfaSalazine, SulfaSomizole, Sul mide, rilopiroX, , , RimcaZOle Hydro fazamet, Hydrochloride, Sulfinosine, Sulfinpyra chloride, Rimexolone, Hydrobromide, rimopro ZOne, Sulfisoxazole, Sulfomyxin, Sulfonterol gin, , Rioprostil, , ripisartan, Hydrochloride, Sulfoxamine, Sulinldac, Sulmarin, Sulnida Risedronate Sodium, risedronic acid, , Risotilide Zole, , Sulofenur, Sulopenem, Suloxifen Oxalate, Hydrochloride, rispenzepine, Risperdal, Risperidone, , Sulprostone, Sultamicillin, Sulthiame, , , ritipenem, , Ritolukast, ritonavir, riza Sulukast, Sumarotene, , Suncillin Sodium, benzoate, Rocastine Hydrochloride, Rocuronium , Suprofen, Suradista, Suramin, Surfomer, Suric Bromide, Rodocaine, , Rogletimide, rohitukine, ainide Maleate, Suritozole, Suronacrine Maleate, Suxemerid rokitamycin, Roletamicide, Rolgamidine, Rolicyprine, Sulfate, Swainsonine, Symakalim, Symclosene, Symetine Rolipram, Rolitetracycline, Rolodine, RomaZarit, romurtide, Hydrochloride, Synthetic glycosaminoglycans, Taciamine Ronidazole, , Ropitoin Hydrochloride, ropiv Hydrochloride, Tacrine Hydrochloride, Tacrolimus, acaine, Ropizine, roquinimex, Rosaramicin, RoSoxacin, Talampicillin Hydrochloride, Taleranol, Talisomycin, talli Rotoxamine, roXaitidine, Roxarsone, , roXithromy mustine, Talmetacin, Talniflumate, Talopram Hydrochlo cin, rubiginone B1, ruboxyl, rufloxacin, rupatidine, Ruta ride, Talosalate, Hydrochloride, Tamoxifen, mycin, ruzadolane, Sabeluzole, Safingol, Safironil, Saintopin, Fumarate, Tamsulosin Hydrochloride, Tan salbutamol, R-, Salcolex, Salethamide Maleate, Salicyl damine Hydrochloride, , tapgen, taprostene, Alcohol, Salicylamide, Salicylate Meglumine, Salicylic Tasosartan, tauromustine, Taxane, Taxoid, Tazadolene Suc Acid, , Salnacedin, Salsalate, Sameridine, Sam cinate, taZanolast, tazaroteine, Tazifylline Hydrochloride, patrilat, Sancycline, Sanfetrinem, Sanguinarium Chloride, TaZobactam, Tazofelone, Hydrochloride, Saperconazole, Saprisartan, Sapropterin, Saquinavir, Sara Tebufelone, Tebuduine, Technetium Tc 99 m Bicisate, Teclo floxacin Hydrochloride, Saralasin Acetate, SarCNU, sarco Zan, Tecogalan Sodium, Teecleukin, , Tegafur, phytol A, SargramoStim, Sarmoxicillin, Sarpicillin, Sar Tegretol, Teicoplanin, , tellurapyrylium, telm pogrelate, Saruplase, Saterinone, Satigrel, Satumomab esteine, telmisartan, telomerase inhibitors, Teloxantrone pendetide, Schick Test Control, Scopafungin, Hydrochloride, Teludipine Hydrochloride, Temafloxacin Hydrobromide, Scrazaipine Hydrochloride, Sdi 1 mimetics, Hydrochloride, Tematropium Methyl sulfate, Temazepam, Secalciferol, , Seelzone, Seglitide Acetate, Sel Temelastine, temocapril, Temocillin, temoporfin, temozolo egiline, Hydrochloride, Selenium Sulfide, Sele mide, Tenidap, Teniposide, tenosal, tenoxicam, tepirindole, nomethionine Se 75, Selfotel, sematilide, Semduramicin, Tepoxalin, Teprotide, teraZOsin, Terbinafine, Semotiadil, Semustine, Sense oligonucleotides, Sepazonium Sulfate, Terconazole, , terflavoxate, , Chloride, Seperidol Hydrochloride, Seprilose, Teriparatide Acetate, terlakiren, terlipressin, , Hydrochloride, Seractide Acetate, Maleate, Teroxalene Hydrochloride, Teroxirone, , Tesicam, Serine, Sermetacin, Sermorelin Acetate, Sertaconazole, Tesimide, , , , tetrachlo , Sertraline, , , Sevirumab, rodecaoxide, Tetracycline, Tetrahydrozoline Hydrochloride, , sezolamide, Sibopirdine, Hydro Tetramisole Hydrochloride, Tetrazolast Meglumine, tetra chloride, Signal transduction inhibitors, , Silipide, Zomine, TetrofoSmin, Tetroquinone, TetroXoprim, Tetry Silteplase, Silver Nitrate, Simendan, SimtraZene, Simvasta damine, thaliblastine, , Theofibrate, Theophyl tin, Sincalide, Sinefungin, Sinitrodil, Sinnabidol, Sipatrigine, line, Thiabendazole, Thiamiprine, , Sirolimus, Sisomicin, Sitogluside, sizofiran, Sobu ZOxane, , Thiazesim Hydrochloride, Thiazinamium Chlo Sodium Amylosulfate, Sodium Iodide I 123, Sodium Nitro ride, , Thimerfonate Sodium, Thimerosal, prusside, , Sodium phenylacetate, Sodium thiocoraline, thiofedrine, Thioguanine, thiomarinol, Thio Salicylate, Solverol, Solypertine Tartrate, Somalapor, pental Sodium, , , Thiotepa, Thio Somantadine Hydrochloride, Somatomedin B, Somatomedin thixene, Thiphenamil Hydrochloride, Thiphencillin Potas C, Somatrem, Somatropin, Somenopor, Somidobove, Soner sium, Thiram, , Threonine, Thrombin, min, Sorbinil, Sorivudine, , Soterenol Hydrochloride, thrombopoietin, thrombopoietin mimetic, thymalfasin, thy Sparfloxacin, Sparfosate Sodium, Sparfosic acid, SparSomy mopoietin receptor agonist, thymotrinan, Thyromedan cin, Sulfate, Spectinomycin Hydrochloride, Spi Hydrochloride, Thyroxine 1 125, Thyroxine 1 131, Tiac camycin D, , Spiradoline MeSylate, Spiramycin, rilast, Tiacrilast Sodium, tiagabine, , , Spirapril Hydrochloride, Spiraprilat, Spirogermanium tiapa?ant, Tiapamil Hydrochloride, Tiaramide Hydrochlo US 2006/OO18933 A1 Jan. 26, 2006

ride, Tiazofurin, Tibenelast Sodium, , Tilbric Acid, ride, Vinblastine Sulfate, citrate, Vincofos, vin Ticabesone Propionate, Ticarbodine, Ticarcillin Cresyl conate, Vincristine Sulfate, Vindesline, Vindesline Sulfate, Sodium, Ticlatone, ticlopidine, Ticrynafen, , Tifu Vinepidine Sulfate, Vinglycinate Sulfate, Vinleurosine Sul rac Sodium, Tigemonam Dicholine, , fate, Vinorelbine, Vinpocetine, Vintoperol, VinXaltine, Vinzo Hydrochloride, Tilidine Hydrochloride, , tilnoprofen lidine Sulfate, Viprostol, Virginiamycin, Viridofulvin, arbamel, Tilorone Hydrochloride, Tiluldronate Disodium, ViroXime, Vitaxin, Volazocine, Voriconazole, Vorozole, VOX tiludronic acid, Timefurone, Timobesone Acetate, Timolol, ergolide, Warfarin Sodium, , Xanomeline, Xan tin ethyl etiopurpurin, Tinabinol, Tinidazole, Tinzaparin Oxate Sodium, Niacinate, Xemilofiban, Xenalipin, Xenbucin, Xilobam, Ximoprofen, Xipamide, Xorphanol Sodium, Tioconazole, , Tiodonium Chloride, Tio Mesylate, Tosylate, Hydrochloride, peridone Hydrochloride, Tiopinac, Hydrochlo Hydrochloride, Xylose, yangambin, Zab ride, Tiotidine, tiotropium bromide, Tioxidazole, Tipentosin icipril, , Zafirlukast, Zalcitabine, , Hydrochloride, Tipredane, Hydrochloride, Tipri , Zaltidine Hydrochloride, Zaltoprofen, Zan nast Meglumine, Tipropidil Hydrochloride, Tiqueside, amivir, Zankiren, , Zantac, Zarirlukast, Zatebra Tiquinamide Hydrochloride, tirandaly digin, Tirapazamine, dine, , Zatosetron Maleate, Zenarestat, Zenazocine tirilazad, tirofiban, tiropramide, titanocene dichloride, Tix MeSylate, Zeniplatin, Zeranol, Zidometacin, Zidovudine, anox, Tixocortol Pivalate, Hydrochloride, Tobra Zifrosilone, Zilantel, Zilascorb, Zileuton, Zimeldine Hydro mycin, , Tocamphyl, Hydrochloride, chloride, Zinc Undecylenate, Zindotrine, Zinoconazole , , Hydrochloride, Tolbuta Hydrochloride, Zinostatin, Hydrochloride, Zin mide, Tolcapone, Tolciclate, Tolfamide, Tolgabide, lamot ViroXime, , Zobolt, Zofenopril Calcium, Zofeno rigine, Tolimidone, Tolindate, Tolimetin, Tolnaftate, Tolpovi prilat, Hydrochloride, Hydrochloride, done 1 131, Tolpyrramide, Tolrestat, Tomelukast, Zoledronie acid, Hydrochloride, , Tomoxetine Hydrochloride, Tonazocine Mesylate, Topira Zolpidem, Zomepirac Sodium, Zometapine, ZonicleZole mate, topotecan, Topotecan Hydrochloride, topSentin, Hydrochloride, , , Zopolrestat, Zorba , Toquizine, toraSemide, toremifene, Torsemide, mycin, Zorubicin Hydrochloride, , Zucapsaicin or ToSifen, ToSufloxacin, totipotent Stem cell factor, Traca its pharmaceutically acceptable Salts thereof. Zolate, trafermin, Tralonide, Hydrochloride, Tra maZoline Hydrochloride, trandolapril, TraneXamic Acid, 0062. As indicated above this portion may comprise Tranilast, Transcainide, translation inhibitors, traXanox, Tra auxiliary excipients Such as for example diluents, binders, Zodone Hydrochloride, Trazodone-HCL, Trebenzomine lubricants, Surfactants, disintegrants, plasticisers, anti-tack Hydrochloride, Trefentanil Hydrochloride, Treloxinate, agents, opacifying agents, pigments, and Such like. AS Will Maleate, Acetate, tretinoin, Triacetin, be appreciated by those skilled in the art, the exact choice of triacetyluridine, Triafungin, Triamcinolone, Triampy Zine excipient and their relative amounts will depend to Some Sulfate, , , Tribenoside, tricaprilin, extent on the final oral dosage form. Tricetamide, Trichlormethiazide, trichohyalin, triciribine, Tricitrates, Triclofenol , Sodium, Tri 0063 Suitable diluents include for example pharmaceu clonide, trientine, Trifenagrel, triflavin, Triflocin, Trifluba tically acceptable inert fillerS Such as microcrystalline cel Zam, Triflumidate, Hydrochloride, Triflu lulose, lactose, Starch, dibasic calcium phosphate, Saccha peridol, Triflu promazine, Triflu promazine Hydrochloride, rides, and/or mixtures of the foregoing. Examples of diluents Trifluridine, Trihexyphenidyl Hydrochloride, , include microcrystalline celluloses Such as those Sold under Hydrochloride, , Trimeprazine Tar the Trade Mark Avicel PH 101, Avicel PH 102, Avicel PH trate, , Trimethaphan Camsylate, Tri 112, Avicel PH 200, Avicel PH301 and Avicel PH 302; methobenzamide Hydrochloride, Trimethoprim, Trime lactose Such as lactose monohydrate, lactose anhydrous and toZine, Trimetrexate, , Trimoprostil, Pharmatose DCL21 (Pharmatose is a Trade Mark), including Trimoxamine Hydrochloride, Triolein 1125, Triolein 1131, anhydrous, monohydrate and Spray dried forms, dibasic Trioxifene Mesylate, Tripamide, Hydro calcium phosphate Such as Emcompress (Emcompress is a chloride, Hydrochloride, Triptorelin, Trisul Trade Mark); mannitol; Pearlitol SD 200 (Pearlitol SD 200 fapyrimidines, Troclosene Potassium, troglitaZone, Trola is a trade mark); Starch, Sorbitol; Sucrose; and glucose. mine, Troleandomycin, trombodipine, trometamol, 0064 Suitable binders include for example starch, povi Hydrochloride, Tropicamide, tropine ester, tro done, hydroxypropylmethylcellulose, pregelatinised Starch, pisetron, trospectomycin, trovafloxacin, troVirdine, Tryp hydroxypropylcellulose and/or mixtures of the foregoing. tophan, Tuberculin, Tubocurarine Chloride, Tubulozole Hydrochloride, tucarcsol, , , Tybam 0065 Suitable lubricants, including agents that act on the ate, tylogenin, Tyropanoate Sodium, , Tyrothricin, flowability of the powder to be compressed are, for example, tyrphostins, ubenimex, , Undecylenic Acid, colloidal slilcon dioxide such as Aerosil 200 (Aerosil is a Uracil Mustard, , Urea, Uredepa, uridine triphos Trade Mark); talc, Stearic acid, magnesium Stearate, calcium phate, Urofollitropin, Urokinase, Ursodiol, Valaciclovir, Stearate and Sodium Stearyl fumarate. Valine, , Valproate Sodium, Valproic Acid, 0066 Suitable disintegrants include for example lightly Valsartan, Vamicamide, Vanadeine, Vancomycin, Vaninolol, crosslinked polyvinyl pyrrollidone, corn Starch, potato Vapi.prost Hydrochloride, Vapreotide, variolin B, Vaso Starch, maize Starch and modified Starches, croScarmellose pressin, Vecuronium Bromide, velaresol, Velnacrine Male Sodium, croSS-povidone, Sodium Starch glycolate and com ate, Venlafaxine, Veradoline Hydrochloride, Veramine, Vera pamil Hydrochloride, verdins, Verilopam Hydrochloride, binations and mixtures thereof. Verlukast, Verofylline, Veroxan, Verteporfin, Vesnarinone, 0067. The amount of release controlling agent(s) to be vexibinol, Vidarabine, vigabatrin, Hydrochlo used in will be determined based on drug release rate etc. US 2006/OO18933 A1 Jan. 26, 2006

0068 The release controlling agents(s) are selected from particles can be done using Oscillating granulator, commi alkyl celluloses, hydroxyalkyl celluloses, cellulose ethers, nuting mill or any other conventional method. The Sieve cellulose esters, nitro celluloses, polymers of acrylic and used for the sizing can have openings from 0.25 mm to 5 methacrylic acids and esters thereof, polyamides, polycar mm. Alternatively the micro matrix particles can be made by bonates, polyalkylenes, polyalkylene glycols, polyalkylene extrusion, Spheronization or by roller compaction. The terephthalates, polyvinyl esters, polyvinylpyrrolidone, micro matrix particles can be coated by a Solution of one or polyglycolides, polysiloxanes and polyurethanes and co more hydrophobic release controlling agents by any known polymers thereof. method, including Spray application. Spraying can be carried out using a fluidized bed coated (preferably Wurster coat 0069. The high water soluble/permeable release control ing), or in a pan coating System. Alternatively the coating of ling agents is Suitably polyvinyl alcohol, polyvinylpyrroli the micro matrix particles with one or more rate controlling done, methylcellulose, hydroxypropylcellulose, hydrox agents can be done by hot melt proceSS using a granulator or ypropylmethyl cellulose or polyethylene glycol, alginates, fluidized bed coated (preferably Wurster coating), or in a pan polyacrylic acids, Xanthun gum or a mixture thereof. coating System. The compression of tablets is carried out on 0070 The low water soluble/permeable release control usual compression machines (e.g. machines of the Manesty, ling agents is Suitably ethylcellulose, cellulose acetate, cel Cadmach or Kilian) The tablets can be made of various sizes lulose propionate (lower, medium or higher molecular and shapes. weight), cellulose acetate propionate, cellulose acetate 0075 Process for manufacturing combination dosage butyrate, cellulose acetate phthalate, cellulose triacetate, poly(methyl methacrylate), poly(ethyl methacrylate), poly form as per instant invention comprising highly Soluble drug (butyl methacrylate), poly(isobutyl methacrylate), and poly as modified release and another active ingredient as imme (hexyl methacrylate). Poly(isodecyl methacrylate), poly diate release or modified release: (lauryl methacrylate), poly(phenyl methacrylate), 0076 Part (A)-Granules comprising highly soluble poly(methyl acrylate), poly(isopropyl acrylate), poly(isobu drug: as described above. tyl actylate), poly(octadecyl acrylate), waxes Such as bees 0077 Part (B)-It may have following options for manu wax, carnauba wax, microcrystalline wax, and OZokerite; facturing of formulation for another active ingredient. fatty alcohols Such as cetoStearyl alcohol, Stearyl alcohol; cetyl alcohol and myristyl alcohol; and fatty acid esterS Such 0078 i)Granules for multilayered or compression coated as glyceryl monoStearate, glyceryl distearate, glycerol tablets-It be manufactured in accordance with usual tech monooleate, acetylated monoglycerides, tristearin, tripalm niques in which the active ingredient(s) and other excipients itin, cetyl esters wax, glyceryl palmitostearate, glyceryl are mixed and granulated by adding Solution of binder in a behenate, and hydrogenated castor oil or a mixture thereof. low or high shear mixer or by fluidized bed granulation. The granulate is dried, preferably in a fluidized bed dryer. The 0071. The non-biodegradable materials are selected from dried granulate is Sieved and mixed with lubricants and but are not limited to Ammonio methacrylate copolymers disintegrants. Alternatively the manufacture of granules of type A and B as described in USP, Polyacrylate dispersion inner portion can be made by direct mixing of the directly 30% as described in Ph. Eur, Polyvinyl acetate dispersion, compressible excipients or by roller compaction. cellulose derivatives Such as ethylcellulose, cellulose acetate waxes. Such as beeSWax, carnauba wax, microcrystalline 0079 ii) Solution or suspension of active ingredient(s)for wax, and OZokerite, fatty alcohols Such as cetostearyl alco drug layering on compact part-Active ingredient(s) can be hol, Stearyl alcohol, cetyl alcohol and myristyl alcohol; and dissolved or suspended in solution of suitable binder(s). This fatty acid esterS Such as glyceryl monoStearate, glyceryl Solution or Suspension can be sprayed or layered over the distearate, glycerol monooleate, acetylated monoglycerides, dosage form prepared as per the invention. Spraying can be triStearin, tripalmitin, cetyl esters wax, glyceryl palmito carried out using a fluidized bed coated, or in a pan coating Stearate, glyceryl behenate, and hydrogenated castor oil. System. 0.072 The mucoadhesive release controlling agents are 0080 C) Tablet Compression Selected from but are not limited to carbopol, Sodium 0081 Suitable tablet presses can be used for single lay carboxymethyl cellulose, hydroxypropyl cellulose, hydrox ered tablets, multilayered tablets or compression coated ypropylmethyl cellulose, hydroxyethyl cellulose, methyl tablets using granules prepared in part A and part B. cellulose, Sodium hyaluronate, gaur gum, Sodium alginate, polycabophil, Starch, dextran or chitosan. 0082) D) Capsule Filling 0083 Compact tablets of highly soluble active ingredient 0.073 Active ingredients especially the poorly soluble and tablets or granules of another active ingredient can be active ingredients mentioned above can be micronized to filled in hard gelatin capsule Shells by using Suitable increase solubility and/or bioavialability. machines. 0.074 The novel modified release dosage form of the present invention can be manufactured by the following BRIEF DESCRIPTION OF THE DRAWINGS procedure: The micro matrix particles can be manufactured in accordance with usual techniques in which the active 0084 FIG. 1(a) is a cross section of coated micro matrix ingredient and one or more hydrophobic release controlling particles prepared by Spheronization and coating for the agents are mixed and granulated by adding Solvent in a low purpose of illustration only. or high shear mixer or by fluidized bed granulator. The 0085 FIG. 1(b) is a cross section of coated micro matrix granulate is dried, preferably in a fluidized bed dryer. The particles prepared by granulation and coating for the purpose dried granulate is sized. The sizing of the micromatrix of illustration only. US 2006/OO18933 A1 Jan. 26, 2006

0.086 FIG. 2 is a plot of % active ingredient versus time for modified release active agent prepared using dual retard -continued technique as described in the present invention and prepared without retard release technique as per examples 1 and 3; For venlafaxine hydrochloride Instrument Apparatus II, USP (Paddle) 0087 FIG. 3 is a plot of% active ingredient versus time Revolution 100/min. for modified release active agent prepared using dual retard Temperature 37 - O.5. C. technique as described in the present invention and prepared Dissolution medium 500 ml water without retard release technique as per examples 2 and 4. For metformin hydrochloride 0088 FIG. 4 is a plot of% active ingredient versus time Instrument Apparatus II, USP (Paddle) for modified release active agent prepared using dual retard Revolution 50/min. technique as described in the present invention and prepared Temperature 37 - O.5. C. without retard release technique as per examples 8 and 11 Dissolution medium 900 m O.1 NHCI respectively. 0089 FIG. 5 is a plot of metformin plasma concentration 0093. The dissolution of high solubility ingredient of the Versus time for formulation prepared as per the invention; formulation of the present invention is achieved not more 0090 FIG. 1(a) and 1(b) show the cross section of the than 50% in 1 hour and from 25 to 90% in six hours. coated micro matrix particles 1 as described in the present invention and having a high Solubility active ingredient 2, 0094. The dissolution of metformin hydrochloride is hydrophobic release controlling agent 3 and a coating of achieved not more than 50% in 1 hour, and from 30 to 90% hydrophobic release controlling agent 4. FIGS. 2 and 3 is in four hours and not less than 65% in 12 hours. show release of high solubility active agent 5 & 6 and 9 & 10 as per example 1 & 2 respectively from a dosage form 0095. After oral administration of a dosage form of the prepared using dual retard technique and release of high present invention the maximum plasma concentration can be solubility active agent 7 & 8 and 11 & 12 as per example 3 achieved between 700 ng/ml and 2500 ng/ml, preferably & 4 respectively from a dosage form prepared without using from 900 ng/ml to 2400 ng/ml and more preferably from dual retard release technique. The total quaritity of the 1000 ng/ml to 2350 ng/ml. The invivo mean dissolution time hydrophobic release controlling agent is Same in all the (MDT) of the dosage form of the present invention is dosage forms inspite of that the figures clearly shows that approximately 4 to 6 hours. The minimum plasma concen dual retard technology significantly reduces the burst effect tration (at 24 hours)of the said dosage form ranges between and effectively controls the release rate of the high solubility 0 and 450 ng/ml after oral administration. active ingredient for prolonged period. FIG. 4 shows release of high solubility active agent 13 & 14 as per example 8 Conclusion : from a dosage form prepared using dual retard technique and release of high solubility active agent 15 & 16 as per 0096. The composition of the micromatrix particles and example 11 from a dosage form prepared without using dual coated micromatrix particles of the dosage form comprising retard release technique. The total quantity of the hydropho niacin is as follows bic release controlling agent is Same in all the dosage forms. Inspite of that the figures clearly show that dual retard technology significantly reduces the burst effect and effec Micro matrix particles tively controls the release rate of the high solubility antidia betic active ingredient for prolonged period. Niacin 75% w/w to 99% w/w Eudragit RS 1% w/w to 25% w/w Coated micro matrix particles DISCRIPTION OF PREFERRED EMBODIMENTS Micro matrix particles Hydrogenated castor oil 0.091 The following examples further illustrate but by no Magnesium stearate means limit the present invention. 0092. The dissolution of novel dosage form of the present 0097. The composition of the micromatrix particles and invention was determined by following method. coated micromatrix particles of the dosage form comprising metformin hydrochloride is as follows For sodium valproate Instrument Apparatus I, USP (basket) Micro matrix particles Revolution 60/min. Temperature 37 - O.5° C. Metformin hydrochloride 75% w/w to 99% w/w Dissolution medium 1000 ml pH 6.8 buffer Eudragit RS 1% w/w to 25% w/w For niacin Coated micro matrix particles Instrument Apparatus I, USP (Basket) Micro matrix particles Revolution 100/min. Hydrogenated castor oil Temperature 37 - O.5° C. Magnesium stearate Dissolution medium 900 m O.1 NHCI US 2006/OO18933 A1 Jan. 26, 2006

DESCRIPTION OF PREFERRED 0108 Tablet (2)-643 mg granules are pressed to tablet EMBODIMENTS (equivalent to 500 mg niacin) using 14.95x8.35 mm oblong punches. EXAMPLES 0109 The dissolution rate of the novel dosage form was Example 1 determined (Table 2) 0098 A) Micro matrix particles-90.91% w/w of sodium TABLE 2 valproate is mixed with 9.09% w/w of Eudragit RS (Ammo nio Methacrylate Copolymer type B USP) and the mixture Dissolution profile is granulated with a Solvent mixture of and meth % Released ylene chloride and then dried. The granules are sized. 0099 B) Coating of Micro matrix particles-85.54% Tablet (1) Tablet (2) W/w of micro matrix particles is charged in fluidized bed 1. 9.1 12.0 2 14.6 18.2 processor. 13.61% w/w of hydrogenated castor oil is dis 4 23.8 28.6 Solved in acetone and this coating Solution is sprayed to coat 6 27.5 35.2 the micro matrix particles. The coated micro matrix particles 8 30.6 39.5 are sieved and mixed with 0.86% w/w magnesium Stearate. 1O 34.7 44.8 12 37.6 49.5 0100 C) Compression of Tablets 14 43.8 52.5 24 50.3 64.5 0101 Tablet (1)-1286 mg granules are pressed to tablet (equivalent to 1000 mg sodium valproate) using 20.3x9.8 mm oval punches. 0110 Dosage forms described in the examples 3 and 4 0102 Tablet (2)-643 mg granules are pressed to are prepared by not coating the micro matrix particles but the tablet(equivalent to 500 mg sodium valproate) using 14.95x hydrophobic release controlling agent is mixed with the 8.35 mm oblong punches. micro matrix particles. The Sole purpose of these examples is to demonstrate the usefulness of the present invention as 0103) The dissolution rate of the novel dosage form was described earlier. The examples clearly show that the rate of determined (Table 1) release of the modified release active ingredient is signifi cantly faster than the present invention. TABLE 1. Dissolution profile Example 3 % Released 0111) 77.76% w/w of sodium valproate is mixed 7.78% w/w of Eudragit RS (Ammonio Methacrylate Copolymer Tablet (1) Tablet (2) type B USP) and the mixture is granulated with a solvent 1. 18.2 23.4 mixture of acetone and methylene chloride and then dried. 2 27.8 35.1 The granules are sized and mixed with 13.6% w/w of 4 42.5 515 hydrogenated castor oil and 0.86% w/w of magnesium 6 52.8 62.9 Stearate. 8 61.6 72.1 1O 68.3 79.2 12 74.2 84.1 0112 Compression of Tablets 14 79.2 88.3 0113 Tablet (1)-1286 mg granules are pressed to tablet 24 94.4 102.0 (equivalent to 1000 mg sodium valproate) using 20.3x9.8 mm oval punches. Example 2 0114 Tablet (2)-643 mg granules are pressed to tablet (equivalent to 500 mg sodium valproate) using 14.95x8.35 0104 A) Micro matrix particles-90.91% w/w of niacin mm oblong punches. is mixed with 9.09% w/w of Eudragit RS (Ammonio Meth acrylate Copolymer type B USP) and the mixture is granu 0115 The dissolution rate of the novel dosage form was lated with a Solvent mixture of acetone and methylene determined (Table 3) chloride and then dried. The granules are sized. 0105 B) Coating of Micro matrix particles-85.54% TABLE 3 W/w of micro matrix particles is charged in fluidized bed Dissolution profile processor. 13.61% w/w of hydrogenated castor oil is dis Solved in acetone and this coating Solution is sprayed to coat % Released the micro matrix particles. The coated micro matrix particles are sieved and mixed with 0.86% w/w magnesium Stearate. Tablet (1) Tablet (2) 1. 63.4 50.2 0106 C) Compression of Tablets 2 85.1 69.1 4 101.6 92.0 0107 Tablet (1)-1286 mg granules are pressed to tablet 6 103.1 102.5 (equivalent to 1000 mg niacin) using 20.3x9.8 mm oval punches. US 2006/OO18933 A1 Jan. 26, 2006

Example 4 0116) 77.76% w/w of niacin is mixed with 7.78% w/w of TABLE 5-continued Eudragit RS (Ammonio Methacrylate Copolymer type B USP) and the mixture is granulated with a solvent mixture Dissolution profile of acetone and methylene chloride and then dried. The Time (hour) % Released granules are sized and mixed with 13.6% w/w of hydroge nated castor oil and 0.86% W/w of magnesium Stearate. 6 50.3 8 62.5 0117 Compression of Tablets 12 68.4 0118 Tablet (1) The granules are pressed to 1286 mg (equivalent to 1000 mg niacin) are compressed using 20.3x 9.8 mm oval punches. Example 6 0119) Tablet (2) The granules are pressed to 643 mg (equivalent to 500 mg niacin) are compressed using 14.95x 0125 A) Micro matrix particles-95.24% w/w of niacin 8.35 mm oblong punches. is mixed with 4.76% w/w of Eudragit RS (Ammonio Meth acrylate Copolymer type B USP) and the mixture is granu 0120) The dissolution rate of the novel dosage form was lated with a Solvent mixture of acetone and methylene determined (Table 4) chloride and then dried. The granules are sized. TABLE 4 0126 B) Coating of Micro matrix particles-92.43% Dissolution profile W/w of micro matrix particles is charged in fluidized bed processor. 6.60% w/w of hydrogenated castor oil is dis % Released Solved in acetone and this coating Solution is sprayed to coat Tablet (1) Tablet (2) the micro matrix particles. The coated micro matrix particles 1. 31.9 29.6 are sieved and mixed with 0.97% w/w magnesium Stearate. 2 44.8 34.9 4 603 51.7 0127 C) Compression of tablets-1136 mg granules are 6 71.7 62.1 pressed to tablet (equivalent to 1000 mg niacin) using 8 81.4 67.7 1O 88.2 74.7 20.3x9.8 mm oval punches. 12 94.7 82.3 24 98.6 98.1 0128. The dissolution rate of the novel dosage form was determined (Table 6) Example 5 TABLE 6 0121 A) Micro matrix particles-80.93% w/w of ven Dissolution profile lafaxine hydrochloride is mixed with 19.07% w/w of Eudragit RS (Ammonio Methacrylate Copolymer type B Time (hour) % Released 24.87 USP) and the mixture is granulated with a solvent mixture 35.25 of acetone and methylene chloride and then dried. The 48.71 granules are sized. 57.80 64.61 0122 B) Coating of Micro matrix particles 70.13% 72.22 W/w of micro matrix particles is charged in fluidized bed 77.20 processor. 28.37% w/w of hydrogenated castor oil is dis Solved in acetone and this coating Solution is sprayed to coat the micro matrix particles. The coated micro matrix particles are Sieved and mixed with 1.0% W/w magnesium Stearate Example 7 and 0.50% w/w colloidal silicon dioxide. 0129 A) Micro matrix particles-Same as example 6. 0123 C) Compression of tablets-299.09 mg granules are pressed to tablet (equivalent to 150 mg venlafaxine) 9.53 0130 B) Coating of Micro matrix particles-90.44% mm round, concave punches. W/w of micro matrix particles is charged in fluidized bed processor. 8.61% w/w of hydrogenated castor oil is dis 0.124. The dissolution rate of the novel dosage form was Solved in acetone and this coating Solution is sprayed to coat determined (Table 5) the micro matrix particles. The coated micro matrix particles TABLE 5 are sieved and mixed with 0.95% w/w magnesium Stearate. Dissolution profile 0131 C) Compression of tablets-1161 mg granules are pressed to tablet (equivalent to 1000 mg niacin) using Time (hour) % Released 20.3x9.8 mm oval punches. 2 32.1 4 4.1.8 0132) The dissolution rate of the novel dosage form was determined (Table 7) US 2006/OO18933 A1 Jan. 26, 2006 18

Solved in acetone and this coating Solution is sprayed to coat TABLE 7 the micro matrix particles. The coated micro matrix particles are sieved and mixed with 0.84% w/w magnesium Stearate. Dissolution profile 0141 C) Compression of Tablets Time (hour) % Released 0142) 1311 mg granules are pressed to tablet (equivalent 24.35 to 1000 mg metformin hydrochloride) using 20.3x9.8 mm 36.41 oval punches. 43.86 50.63 0143. The dissolution rate of the novel dosage form was 57.43 63.82 determined (Table 9) 71.20 TABLE 9 Dissolution profile Example 8 Time (hour) % Released 0133) A) Micro matrix particles-90.91% w/w of met 1. 33.44 formin hydrochloride is mixed with 9.09% w/w of Eudragit 2 45.79 RS (Ammonio Methacrylate Copolymer type B USP)and 4 55.28 the mixture is granulated with a Solvent mixture of acetone 6 60.45 and methylene chloride and then dried. The granules are 8 66.10 sized. 1O 69.87 12 73.88 0134 B) Coating of Micro matrix particles-85.54% 24 86.97 W/w of micro matrix particles is charged in fluidized bed processor. 13.61% w/w of hydrogenated castor oil is dis Solved in acetone and this coating Solution is sprayed to coat 0144 A) Micro matrix particles-90.91% w/w of met the micro matrix particles. The coated micro matrix particles formin hydrochloride is mixed with 9.09% w/w of Eudragit are sieved and mixed with 0.86% w/w magnesium Stearate. RS (Ammonio Methacrylate Copolymer type B USP) and the mixture is granulated with a Solvent mixture of acetone 0135 C) Compression of Tablets and methylene chloride and then dried. The granules are 0136 Tablet (1)-1286 mg granules are pressed to tablet sized. (equivalent to 1000 mg metformin hydrochloride) are com 0145 B) Coating of Micro matrix particles-87.23% pressed using 20.3x9.8 mm oval punches. W/w of micro matrix particles is charged in fluidized bed 0137 Tablet (2)-643 mg granules are pressed to tablet processor. 11.90% w/w of hydrogenated castor oil is dis (equivalent to 500 mg metformin hydrochloride) are com Solved in acetone and this coating Solution is sprayed to coat pressed using 14.95x8.35 mm oblong punches. the micro matrix particles. The coated micro matrix particles 0.138. The dissolution rate of the novel dosage form was are sieved and mixed with 0.87% w/w magnesium Stearate. determined (Table 8) 0146 C) Compression of Tablets 0147 1261 mg granules are pressed to tablet (equivalent TABLE 8 to 1000 mg metformin hydrochloride) using 20.3x9.8 mm Dissolution profile oval punches. 0.148. The dissolution rate of the novel dosage form was % Released determined (Table 10) Tablet (1) Tablet (2) TABLE 10 1. 37.1 36.5 2 49.5 51.O Dissolution profile 4 65.3 63.6 6 76.2 77.5 Time (hour) % Released 8 84.O 87.8 1O 91.7 91.9 42.1 12 98.9 95.8 51.30 66.60 78.8O 84.60 Example 9 91.OO 99.70 0139 A) Micro matrix particles-90.91% w/w of met formin hydrochloride is mixed with 9.09% w/w of Eudragit RS (Ammonio Methacrylate Copolymer type B USP) and 0149 Dosage forms described in the example 11 are the mixture is granulated with a Solvent mixture of acetone prepared by not coating the micro matrix particles but the and methylene chloride and then dried. The granules are hydrophobic release controlling agent is mixed with the sized. micro matrix particles. The Sole purpose of these examples is to demonstrate the usefulness of the present invention as 014.0 B) Coating of Micro matrix particles-83.91% described earlier. The examples clearly show that the rate of W/w of micro matrix particles is charged in fluidized bed release of the modified release antidiabetic active ingredient processor. 15.26% w/w of hydrogenated castor oil is dis is significantly faster than the present invention. US 2006/OO18933 A1 Jan. 26, 2006

Example 11 0150) 77.76% w/w of metformin hydrochloride is mixed TABLE 12-continued with 7.78% w/w of Eudragit RS (Ammonio Methacrylate Dissolution profile Copolymer type B USP) and the mixture is granulated with a Solvent mixture of acetone and methylene chloride and Time (hour) % Released then dried. The granules are sized and mixed with 13.6% 8 86.15 w/w of hydrogenated castor oil and 0.86% w/w of magne 1O 88.48 sium Stearate. 12 93.30 0151 Compression of Tablets Example 13 0152 Tablet (1)-1286 mg granules are pressed to tablet (equivalent to 1000 mg metformin hydrochloride) using 0160 A) Micro matrix particles-Same as of example 20.3x9.8 mm oval punches. 12. 0153 Tablet (2)-643 mg granules are pressed to tablet 0161 B) Coating of Micro matrix particles-88.70% (equivalent to 500 mg metformin hydrochloride) using W/w of micro matrix particles is charged in fluidized bed 14.95x8.35 mm oblong punches. processor. 10.31% w/w of hydrogenated castor oil is dis Solved in acetone and this coating Solution is sprayed to coat 0154) The dissolution rate of the novel dosage form was the micro matrix particles. The coated micro matrix particles determined (Table 11) are sieved and mixed with 0.99% w/w magnesium Stearate. TABLE 11 0162 C) Compression of Tablets 0163) 1212 mg granules are pressed to tablet (equivalent Dissolution profile to 1000 mg metformin hydrochloride) using 20.3x9.8 mm % Released oval punches. 0164. The dissolution rate of the novel dosage form was Tablet (1) Tablet (2) determined (Table 13) 1. 50.3 52.5 2 70.5 74.2 TABLE 13 4. 88.0 89.4 6 100.9 100.7 Dissolution profile Time (hour) % Released 31.84 Example 12 44.66 50.55 O155 A) Micro matrix particles-93.02% w/w of met 65.29 formin hydrochloride is mixed with 6.98% w/w of Eudragit 73.29 RS (Ammonio Methacrylate Copolymer type B USP) and 79.8O the mixture is granulated with a Solvent mixture of acetone 85.90 and methylene chloride and then dried. The granules are sized. Example 14 0156 B) Coating of Micro matrix particles-90.56% 0165 A) Micro matrix particles-Same as of example W/w of micro matrix particles is charged in fluidized bed 12. processor. 8.42% W/w of hydrogenated castor oil is dis 0166 B) Coating of Micro matrix particles-92.51% Solved in acetone and this coating Solution is sprayed to coat W/w of micro matrix particles is charged in fluidized bed the micro matrix particles. The coated micro matrix particles processor. 6.45% w/w of hydrogenated castor oil is dis are Sieved and mixed with 1.01% W/w magnesium Stearate. Solved in acetone and this coating Solution is sprayed to coat O157 C) Compression of Tablets the micro matrix particles. The coated micro matrix particles 0158 1187 mg granules are pressed to tablet (equivalent are sieved and mixed with 1.03% w/w magnesium Stearate. to 1000 mg metformin hydrochloride) using 20.3x9.8 mm 0167 C) Compression of Tablets oval punches. 0168 1162 mg granules are pressed to tablet (equivalent 0159. The dissolution rate of the novel dosage form was to 1000 mg metformin hydrochloride) using 20.3x9.8 mm determined (Table 12) oval punches. 0169. The dissolution rate of the novel dosage form was TABLE 12 determined (Table 14) Dissolution profile TABLE 1.4 Time (hour) % Released Dissolution profile 37.59 Time (hour) % Released 48.91 59.24 1. 45.90 74-85 2 60.10 US 2006/OO18933 A1 Jan. 26, 2006

Test Formulation, Dose and Mode of Administration: TABLE 14-continued 0180 Test Formulation: 1000 mg Metformin sustained Dissolution profile release (SR) formulation prepared as per the invention disclosed. Volunteers received a single oral dose of the Time (hour) % Released above product with 200 ml of water 30 minutes after a 4 77.00 following high calorie breakfast (-800 Kcal). 6 89.70 8 96.72 : 1O 98.57 0181. The following Pharmacokinetic parameters were 12 104.33 calculated using non compartments methods: the area under the drug plasma concentration curve from time of dosing to Example 15 the time of last sampling point (AUCo.); the area under the 0170 A) Micro matrix particles-Same as of example drug plasma concentration verSuS time curve extrapolated to 12. infinity (AUConne); the maximum measured concentration 0171 B) Coating of Micro matrix particles-91.33% of the drug in the plasma (C) and the time at which this W/w of micro matrix particles is charged in fluidized bed concentration was measured (t) ; the concentration at 24 processor. 7.65% w/w of hydrogenated castor oil is dis hours (C); the time taken for drug plasma concentration Solved in acetone and this coating Solution is sprayed to coat to decrease by 50% (t) ; and the terminal first-order the micro matrix particles. The coated micro matrix particles elimination rate constant (K). are Sieved and mixed with 1.02% W/w magnesium Stearate. 0182 Area Under the curve (AUC) is the integral part of drug blood level over time from zero to infinity and is a 0172 C) Compression of Tablets measure of quantity of drug absorbed and in the body. 0173 1177 mg granules are pressed to tablet (equivalent 0183 AUC(0-t) represents area under the curve from to 1000 mg metformin hydrochloride) using 20.3x9.8 mm Zero to time t, where t represents the time at which last blood oval punches. Sample was taken. 0.174. The dissolution rate of the novel dosage form was 0184 AUC of represents area under the curve from determined (Table 15) Zero to infinity. TABLE 1.5 0185 Elimination half life of a drug is the time in hours Dissolution profile necessary to reduce the drug concentration in the blood, Time (hour) % Released plasma or Serum to /2 after equilibrium is reached. 44.OO 0186 C is the peak plasma concentration achieved 58.8O after the administration of the drug. 71.30 84.10 0187 T is the time to reach peak plasma concentra 91.93 tion. 95.34 98.59 Statistical Methods: 0188 Descriptive statistics of relevant Pharmacokinetic Example 16 parameters were performed. Establishing the Pharmacokinetic Profile of Metformin Sus Methods Used for Analysis of Metformin in Plasma tained Release Formulation Samples: 0.175. The study was carried out to evaluate the pharma 0189 Estimation of Metformin in plasma samples was cokinetic parameters of the Sustained release metformin carried out by High Performance Liquid Chromatography formulation prepared as per the examples described above. and UV detection at 234 nm. Briefly 0.5 ml of plasma Methodology: Sample was precipitated with 2.0 ml acetonitrile. Samples were centrifuged and Supernatant aliquot was washed with 0176) The biostudy had an open label, single period, . After centrifugation, aqueous layer was Single treatment, Single dose Study design. injected on HPLC. 0177. Non-compartmental Pharmacokinetic assessment Pharmacokinetic Results: was based on the plasma levels of metformin. Blood Samples were obtained before dosing and at the following times after 0190. The summary of the Pharmacokinetic parameters is administration of test formulation; Pre-dose, 0.5,0.75, 1.0, contained in Table 16. The mean plasma concentration 1.5, 2.0, 3.0, 3.5, 4.0, 5.0, 6.0, 8.0, 10.0, 12.0, 15.0, 18.0, and versus time curve is depicted in FIG. 5. 24.0 hours. TABLE 16 Study Population: Pharmacokinetic Parameters - 0.178 Healthy male volunteers aged between 18 to 45 Metformin SR (1000 mg yearS. Parameters Unit Test (Meant SD) Number of Subjects: AUCo inf ng * hr/ml 18776 4672 0179 Four (04) volunteers were enrolled and all of them AUCo. 2 ng * hr/ml 15424 - 3428 completed the study. All 04 volunteers were included in the Cmax ng/ml 1348 116 Pharmacokinetic and Safety analyses. US 2006/OO18933 A1 Jan. 26, 2006 21

2. A dosage form as claimed in claim 1, is in the form of TABLE 16-continued tablet. Pharmacokinetic Parameters - 3. A dosage form according to claim 1, wherein the Metformin SR (1000 mg hydrophobic release controlling agents are Selected from the group comprising of ammonio methacrylate copolymers Parameters Unit Test (Mean + SD) type A and B as described in USP, methacrylic acid copoly C24 h ng/ml 245 - 90 mer type A, B and C as described in USP, polyacrylate Tmax hir 4.88 - 1.03 dispersion 30% as described in Ph. Eur., polyvinyl acetate T1/2 hir 9.28 - 1.73 dispersion, ethylcellulose, cellulose acetate, cellulose pro pionate (lower, medium or higher molecular weight), cellu lose acetate propionate, cellulose acetate butyrate, cellulose Conclusion: acetate phthalate, cellulose triacetate, poly(methyl meth 0191 Metformin has shown Sustained release character acrylate), poly(ethyl methacrylate), poly(butyl methacry istics with following Pharmacokinetic profile; late), poly(isobutyl methacrylate), poly(hexyl methacrylate), poly(isodecyl methacrylate), poly lauryl methacrylate), 0192 The AUC ranged from 12395 to 20345 nghr/ poly(phenyl methacrylate), poly(methyl acrylate), poly(iso ml. propyl acrylate), poly(isobutyl actylate), poly(octadecyl 0193 The AUC ranged from 15791 to 25727 nghr/ acrylate), waxes Such as beeswax, carnauba wax, microc ml. rystalline wax, and OZokerite; fatty alcohols Such as ceto 0194 The C ranged from 1227 to 1452 ng/ml. Stearyl alcohol, Stearyl alcohol, cetyl alcohol and myristyl alcohol; and fatty acid esterS Such as glyceryl monoStearate; 0195 The C ranged from 165 to 373 ng/ml. glycerol monooleate, acetylated monoglycerides, triStearin, 0196) The T ranged from 3.50 to 6.00 hours. tripalmitin, cetyl esters wax, glyceryl palmitostearate, glyc eryl behenate and hydrogenated castor oil. 0197) The T ranged from 7.13 to 11.19 hours. 4. A dosage form according to claim 3, wherein Said hydrophobic release controlling agents are Selected prefer Example 17 ably from ammonio methacrylate co-polymers. 0198 1) Production of Inner Portion 5. A dosage form according to claim 4, wherein preferred 0199 69.61% w/w of Aspirin coated granules (Aspirin ammonio methacrylate co-polymers are selected from 96% w/w, 2.0% w/w hydrogenated castor oil & 2.0% w/w Eudragit RS (Ammonio Methacrylate Copolymer type B citric acid anhydrous coated) mixed with the mixture of USP), Eudragit RL (Ammonio Methacrylate Copolymer 11.56% w/w of microcrystalline cellulose (PH112, dried), type A USP) and Eudragit NE30D (Polyacrylate dispersion 7.17% w/w sodium starch Glycolate (dried), 2.24% w/w 30% Ph. Eur). citric acid anhydrous, 4.48% w/w talc, 1.79% w/w colloidal 6. A dosage form according to claim 1,wherein in micro silicon dioxide, 1.79% w/w Stearic acid and 1.35% w/w matrix particles, the active ingredient and one or more hydrogenated vegetable oil. hydrophobic release controlling agents are present in a ratio of from 100:1 to 100:75. 0200) 2) Production of Outer Portion 7. A dosage form according to claim 6,wherein in micro 0201 A) Micro matrix particles-93.02% w/w of nico matrix particles, the active ingredient and one or more tinic acid is mixed with 6.98% w/w of Eudragit RS PO hydrophobic release controlling agents are present prefer (Ammonio Methacrylate Copolymer type B USP) and the ably in a ratio of from 100:2.5 to 100:50. mixture is granulated with a Solvent mixture of acetone and 8. A dosage form according to claim 6,wherein in micro methylene chloride and then dried. The granules are sized matrix particles, the active ingredient and one or more through 1.0 mm Screen. hydrophobic release controlling agents are present more 0202 B) Coating of Micro matrix particles—92.67% preferably in a ratio of from 100:2.5 to 100:30. W/w of micro matrix particles is charged in fluidized bed 9. A dosage form according to claim 6,wherein in micro processor. 6.47% w/w of hydrogenated castor oil is dis matrix particles, the active ingredient and one or more Solved in acetone and this coating Solution is sprayed to coat hydrophobic release controlling agents are present most the micro matrix particles. The coated micro matrix particles preferably in a ratio of from 100:2.5 to 100:20. are sieved and mixed with 0.86% w/w magnesium Stearate. 10. A dosage form according to claim 1, wherein in micro 0203 3) Compression of Bilayered Tablets matrix particles, the active ingredient can be less than or 0204 483.17 mg granules of inner portion (equal to 325.0 equal to 1500 mg. mg aspirin) and 1160 mg granules of outer portion (equal to 11. A dosage form according to claim 1, wherein the 1000 mg nicotinic acid) are compressed into bilayered hydrophobic release controlling agents employed for coat tablets using 20.3x9.8 mm oblong shaped punches. ing the Said micromatrix particles are Selected from the group comprising of ammonio methacrylate copolymers What is claimed is: type A and B as described in USP, methacrylic acid copoly 1. A modified release dosage form comprising of a high mer type A, B and C as described in USP, polyacrylate Solubility active ingredient prepared by using dual retard dispersion 30% as described in Ph. Eur., polyvinyl acetate technique to control the release of the high Solubility active dispersion, ethylcellulose, cellulose acetate, cellulose pro ingredient, said dosage form comprising a) micro matrix pionate (lower, medium or higher molecular weight), cellu particles and one or more hydrophobic release controling lose acetate propionate, cellulose acetate butyrate, cellulose agent and b) coating of one or more hydrophobic release acetate phthalate, cellulose triacetate, poly(methyl meth controling agent on Said micro matrix particles. acrylate), poly(ethyl methacrylate), poly(butyl methacry US 2006/OO18933 A1 Jan. 26, 2006 22 late), poly(isobutyl methacrylate), poly(hexyl methacrylate), nist; Serotonin antagonist; Serotonin inhibitor, Serotonin poly(isodecyl methacrylate), poly(lauryl methacrylate), receptor antagonist; Steroid; thyroid hormone; thyroid poly(phenyl methacrylate), poly(methyl acrylate), poly(iso inhibitor; thyromimetic, tranquilizer; amyotrophic lateral propyl acrylate), poly(isobutyl actylate), poly(octadecyl Sclerosis agent; cerebral ischemia agent, Paget's disease acrylate), waxes Such as beeswax, carnauba wax, microc rystalline wax, and OZokerite; fatty alcohols Such as ceto agent; unstable angina agent; vasoconstrictor; vasodilator; Stearyl alcohol, Stearyl alcohol, cetyl alcohol and myristyl wound healing agent, Xanthine oxidase inhibitor and the alcohol; and fatty acid esterS Such as glyceryl monoStearate; like. glycerol monooleate, acetylated monoglycerides, triStearin, 18. A dosage form according to claim 1, wherein the high tripalmitin, cetyl esters wax, glyceryl palmitoStearate, glyc Solubility active ingredient is Selected from the group com eryl behenate and hydrogenated castor oil. prising of Abacavir Sulfate; Aminocaproic acid; Alendronate 12. A dosage form according to claim 11, wherein the Sodium; Amitriptyline hydrochloride, Amphetamine; hydrophobic release controlling agents is Selected from fatty Acetaminophen; Atropine Sulfate, Balsalazide, BenZepril acid esters. hydrochloride; Bisoprolol fumarate; Bupropion hydrochlo 13. A dosage form according to claim 12, wherein the ride; Buformin; Captopril; Cetrizine hydrochloride; Cipro hydrophobic release controlling agents are Selected from the floxacin; Clindamycin; Chlorpheniramine maleate; Chlor group comprising of hydrogenated castor oil and glycerol promazine hydrochloride; Clomipramine hydrochloride; distearate. Clonidine hydrochloride; Clopidogrel bisulfate; Cloxacillin 14. A dosage form according to claim 1, micro matrix Sodium, Codeine phosphate, Colchicines, Cyclophospha particles and coating of one or more hydrophobic release mide; Diethylcarbamazine citrate; DL-methionine; Ethem controlling agents are present in a ratio of from 100:0.5 to butol hydrochloride; Eprosartan; Ethosuximide; Erythromy 100:75. cin; Ferrous sulfate; Fluoxetine hydrochloride; Fosinopril 15. A dosage form according to claim 14, wherein micro Sodium; Gabapentin; Hydralazine hydrochloride; Hydroc matrix particles and coating of one or more hydrophobic odone bitartrate; Hydroxyzine hydrochloride; Hydroxyurea; release controlling agents are preferably present in a ratio of Indinavir Sulfate; Isoniazid, ISOSorbide moninitrate; Lacto from 100:1 to 100:50. bionate; Lamivudine; Levamisole hydrochloride; Levof 16. A dosage form according to claim 14, wherein micro loxacin; Lisinopril; LOSartan potassium; Metformin hydro matrix particles and coating of one or more hydrophobic release controlling agents are more preferably present in a chloride; Methylphenidate hydrochloride; Metoprolol ratio of from 100:2.5 to 100:20. tartrate; Minocycline hydrochloride; Montelukast sodium; 17. A dosage form according to claim 1, wherein the high Naproxen Sodium; NeoStigmine bromide, Nicotinamide; Solubility active ingredient is Selected from the group com Niacin; Nifurtimox; Nortriptyline hydrochloride; Olan prising of adrenergic agent, adrenocortical Steroid; adreno Zepine; Oxybytynin chloride; Penicillamine; Penicillin V cortical Suppressant, aldosterone antagonist, amino acid; potassium; Phenytoin sodium; Phenformin; Pravastatin anabolic; analeptic, analgesic, anesthetic, anorectic, anti Sodium; Potassium chloride, Primaquine phosphate; acne agent, anti-adrenergic, anti-allergic, anti-amebic, anti Promethazine; Promethazine hydrochloride; Proponolol anemic, anti-anginal; anti-arthritic, anti-asthmatic, anti-ath hydrochloride; Propoxyphene hydrochloride; Pseudophe erosclerotic, antibacterial; anticholinergic, anticoagulant; drine hydrochloride; Pyridostigmine bromide; Pyridoxine anticonvulsant, antidepressant, antidiabetic, antidiarrheal; hydrochloride; Quinapril hydrochloride, Quetiapine, Rami antidiuretic, anti-emetic, anti-epileptic, antifibrinolytic, pril; Ranitidine hydrochloride; Risedronate Sodium; antifungal, antihemorrhagic, antihistamine; antihyperlipi RosiglitaZone maleate, Sodium Valproate, Salbutamol Sul demia; antihypertensive, antihypotensive; anti-infective; fate; Stavudine, Sumatriptan Succinate; TeraZoSin hydro anti-inflammatory; antimicrobial; antimigraine; antimitotic, chloride; Tetracycline hydrochloride; Timolol meleate; Tra antimycotic, antinauseant, antineoplastic, antineutropenic, modol hydrochloride; Valacyclovir hydrochloride; antiparasitic, antiproliferative; antipsychotic, antirheumatic; Vancomycin; Venlafaxine hydrochloride; Verapamil hydro antiseborrheic, antisecretory; antispasmodic, antithrom chloride; Wafarin Sodium acetylsalicylic acid, acyclovir, botic, anti-ulcerative; antiviral; appetite SuppreSSant; blood allopurinol; amlodipine beSylate; amoxicillin; atenolol, ator glucose regulator, bone resorption inhibitor, bronchodilator; vastatin calcium; azithromycin; carbidopa; carisoprodol; cardiovascular agent, cholinergic, depressant, diagnostic cefprozil; celecoxib, cephalaxin, cimetidine, citalopram aid; diuretic, dopaminergic agent; estrogen receptor agonist, hydrobromide; clindamycin hydrochloride, cyclobenzaprine fibrinolytic, fluorescent agent, free oxygen radical Scaven ger; gastric acid SupreSSant; gastrointestinal motility effec hydrochloride; desloratidine, doxazosin meSylate, doxycy tor; glucocorticoid; hair growth Stimulant; hemostatic; his cline, enalapril maleate; famotidine, feXofenadine hydro tamine H2 receptor antagonists, hormone; chloride; fluconazole; folic acid; irbesartan; levodopa, hypocholesterolemic, hypoglycemic, hypolipidemic, levonorgestrel; levothyroxine Sodium, lorazepam, meclizine hypotensive; imaging agent, immunizing agent; immuno hydrochloride; metaxalone; metronidazole; mirtazepine; modulator; immunoregulator; immunostimulant; immuno nitrofurantoin, nyStatin, oxycodone hydrochloride, parac SuppreSSant; keratolytic, LHRH agonist, mood regulator; etamol, paroxetine hydrochloride; prednisolone quetiapine mucolytic, mydriatic, nasal decongestant; neuromuscular fumerate; raloxifene, hydrochloride; risperidone, Sertraline blocking agent; neuroprotective, NMDA antagonist; non hydrochloride; Sildenafil citrate, Simvastatin, tamoxifen cit hormonal Sterol derivative, plasminogen activator, platelet rate; tamsulosin hydrochloride; temazepam, tolterodine tar activating factor antagonist, platelet aggregation inhibitor; trate; topiramate; traZodone hydrochloride, trimethoprim; psychotropic, radioactive agent; Scabicide, Sclerosing agent; Valsartan; Zolpidem tartrate;or pharmaceutically acceptable Sedative, Sedative-hypnotic, Selective adenosine Al antago salts thereof. US 2006/OO18933 A1 Jan. 26, 2006 23

19. A dosage form according to claim 1, wherein the agonist, mood regulator, mucolytic, mydriatic, nasal decon dissolution of high Solubility active ingredient is not more gestant; neuromuscular blocking agent; neuroprotective; than 50% in 1 hour and from 25 to 90% is released in six NMDA antagonist; non-hormonal sterol derivative; plasmi hours. nogen activator, platelet activating factor antagonist, platelet 20. A dosage form according to claim 1, wherein it aggregation inhibitor, psychotropic, radioactive agent; reduces the chances of dose dumping, unnecessary burst Scabicide, Sclerosing agent, Sedative, Sedative-hypnotic, effects and failure of the system. 21. A dosage form according to claim 1, can be given Selective adenosine Al antagonist; Serotonin antagonist; twice a day or more preferably can be given once a day. Serotonin inhibitor, Serotonin receptor antagonist; Steroid; 22. A dosage form according to claim 1, is used for human thyroid hormone; thyroid inhibitor; thyromimetic, tranquil beings. izer, amyotrophic lateral Sclerosis agent, cerebral ischemia 23. A dosage form according to claim 1, wherein the high agent, Paget's disease agent; unstable angina agent; VaSO Solubility active ingredient is niacin. constrictor; vasodilator, wound healing agent; Xanthine oxi 24. A modified release dosage form according to claim 1, dase inhibitor and the like. wherein the composition of the micromatrix particles and 29. A dosage form as claimed in claim 28, wherein coated micromatrix particles is as follows another active ingredient is Selected from the group com prising of 16-alpha fluorocStradiol, 16alpha-gitoxin, 16-epi estriol, 17 alpha dihydroeduilenin, 17 alpha estradiol, 17 beta estradiol, 17 hydroxy progesterone, 1alpha-hydroxyvi Micro matrix particles tamin D2, 1-dodecpyrrolidinone, 20-epi-1,25dihydroxyvita Niacin 75% w/w to 99% w/w min D3, 22-oxacalcitriol, 2CVV, 2-nor-cGMP, 3-isobutyl Eudragit RS 1% w/w to 25% w/w GABA, 5-ethynyluracil, 6-FUDCA, 7-methoxytacrine, Coated micro matrix particles Abamectin, abanoquil, abecarnil, abiraterone, Ablukast, Micro matrix particles Ablukast Sodium, Acadesine, acamproSate, Acarbose, Ace Hydrogenated castor oil butolol, Acecainide Hydrochloride, Aceclidine, aceclofenae, Magnesium stearate AcedapSone, Aceglutamide Aluminum, Acemannan, Acetaminophen, Acetazolamide, Acetohexamide, Acetohy droxamic Acid, acetomepregenol, Acetophenazine Maleate, 25. A dosage form according to claim 1, wherein the high AcetoSulfone Sodium, Acetylcholine Chloride, Acetylcys Solubility active ingredient is Sodium Valproate. teine, acetyl-L-carnitine, acetylmethadol, Acifran, acipimox, 26. A process for the preparation of a modified release acitemate, Acitretin, Acivicin, Aclarubicin, aclatonium, dosage form comprising a) preparing a micro matrix par Acodazole Hydrochloride, aconiazide, Acrisorcin, Acrivas ticles containing high Solubility active ingredient and one or tine, Acronine, Actisomide, Actodigin, Acyclovir, acylful more hydrophobic release controlling agent and b) coating Vene, adafenoxate, adapalene, Adapalene, adatanserin, Ada the Said micromatrix particles containing high Solubility tanserin Hydrochloride, adecypenol, adecypenol, Adefovir, active ingredient and one or more hydrophobic release adelmidrol, ademetionine, Adenosine, , controlling agent. Adipheinine Hydrochloride, adiposin, Adozelesin, adrafinil, 27. A dosage form as claimed in claim 1, wherein Said Adrenalone, airbutamine, alacepril, Alamecin, Alanine, Ala dosage form can optionally comprise another active ingre proclate, alaptide, Albendazole, albolabrin, Albuterol, Albu dient as immediate release form or modified release form. toin, Alclofenae, Alclometasone Dipropionate, Alcloxa, 28. A dosage form as claimed in claim 27 wherein another aldecalmycin, Aldesleukin, Aldioxa, Alendronate Sodium, active ingredient is Selected from the group comprising of alendronic acid, alentemol, Alentemol Hydrobromide, Ale adrenergic agent, adrenocortical Steroid; adrenocortical Sup tamine Hydrochloride, Aleuronium Chloride, Alexidine, preSSant; aldosterone antagonist; amino acid; anabolic; ana alfacalcidol, Alfentanil Hydrochloride, alfuZosin, AlgeStone leptic, analgesic, anesthetic; anorectic, anti-acne agent, anti Acetonide, alglucerase, Aliflurane, alinastine, Alipamide, adrenergic, anti-allergic, anti-amebic, anti-anemic, anti Allantoin, Allobarbital, Allopurinol, ALL-TK antagonists, anginal; anti-arthritic, anti-asthmatic, anti-atherOSclerotic, Alonimid, aloSetron, Alosetron Hydrochloride, Alovudine, antibacterial; anticholinergic, anticoagulant; anticonvulsant, Alpertine, Alpha Amylase, alpha idoSone, Alpidem, Alpra antidepressant, antidiabetic, antidiarrheal; antidiuretic, anti Zolam, Alprenolol Hydrochloride, Alprenoxime Hydrochlo emetic, anti-epileptic, antifibrinolytic, antifungal; antihem ride, Alprostadil, Alrestatin Sodium, Altanserin Tartrate, orrhagic, antihistamine, antihyperlipidemia; antihyperten Alteplase, Althiazide, Altretamine, altromycin B, Alverinc Sive, antihypotensive; anti-infective, anti-inflammatory; Citrate, Alvircept Sudotox, Amadinone Acetate, Amantadine antimicrobial; antimigraine; antimitotic, antimycotic, antin Hydrochloride, ambamustine, Ambomycin, Ambruticin, auseant, antineoplastic, antineutropenic, antiparasitic; anti Ambuphylline, AmbuSide, Amcinafal, Amcinonide, Amdi proliferative; antipsychotic, antirheumatic, antiseborrheic, nocillin, Amdinocillin Pivoxil, Amedalin Hydrochloride, antisecretory; antispasmodic, antithrombotic, anti-ulcer amelometasone, Ameltolide, AmeSergide, Ametantrone Acetate, ameZinium metilsulfate, amfebutamone, Amfenac ative; antiviral; appetite Suppressant, blood glucose regula Sodium, Amflutizole, Amicycline, Amidephrine MeSylate, tor, bone resorption inhibitor; bronchodilator; cardiovascu amidox, Amifloxacin, amifostine, Amikacin, Amiloride lar agent, cholinergic, depressant, diagnostic aid; diuretic, Hydrochloride, Aminacrine Hydrochloride, Aminobenzoate dopaminergic agent; estrogen receptor agonist, fibrinolytic, Potassium, Aminobenzoate Sodium, Aminocaproic Acid, fluorescent agent, free oxygen radical Scavenger; gastric Aminoglutethimide, Aminohippurate Sodium, aminole acid SupreSSant; gastrointestinal motility effector; glucocor Vulinic acid, Aminophylline, Aminorex, AminoSalicylate ticoid; hair growth Stimulant, hemostatic; histamine H2 Sodium, AminoSalicylic acid, Amiodarone, Amiprilose receptor antagonists, hormone; hypocholesterolemic, Hydrochloride, Amiquinsin Hydrochloride, amisulpride, hypoglycemic, hypolipidemic, hypotensive; imaging agent; Amitraz, Amitriptyline Hydrochloride, AmlexanoX, amlo immunizing agent, immunomodulator; immunoregulator; dipine, Amobarbital Sodium, Amodiaquine, Amodiaquine immunostimulant; immunosuppressant, keratolytic, LHRH Hydrochloride, Amorolfine, Amoxapine, Amoxicillin, US 2006/OO18933 A1 Jan. 26, 2006 24

Amphecloral, Amphetamine Sulfate, Amphomycin, Ampho Hydrochloride, Biapenem, Bicalutamide, Biciifadine Hydro tericin B, Ampicillin, ampiroXicam, AmpyZine Sulfate, chloride, Biclodil Hydrochloride, Bidisomide, bifemelane, Amguinate, Amrinone, amrinone, amrubicin, Amsacrine, Bifonazole, bimakalim, bimithil, Bindarit, Biniramycin, amylin, amythiamicin, AnageStone Acetate, anagrelide, binoSpirone, bioxalomycin alpha2, Bipenamol Hydrochlo Anakinra, ananain, anaritide, Anaritide Acetate, Anastro ride, Biperiden, Biphenamine Hydrochloride, biriperone, Zole, Anazolene Sodium, Ancrod, andrographolide, Andros bisantrene, bisaramil, bisaZiridinylspermine, bis-benzimida tenedione, angiogenesis inhibitors, Angiotensin Amide, Ani Zole A, bis-benzimidazole B, bisnafide, Bisobrin Lactate, doXime, Anileridine, Anilopam Hydrochloride, Aniracetam, Bisoprolol, Bispyrithione Magsulfex, bistramide D, bistra Anirolac, Anisotropine Methylbromide, Anistreplase, Ani mide K, bistratene A, Bithionolate Sodium, Bitolterol Mesy traZafen, anordrin, antagonist D, antagonist G, antarelix, late, Bivalirudin, Bizelesin, Bleomycin Sulfate, Bolandiol Antazoline Phosphate, Anthelmycin, Anthralin, Anthramy Dipropionate, Bolasterone, , bol cin, antiandrogen, AcedapSone, Felbamate, antiestrogen, dine, Bolenol, Bolmantalate, bopindolol, Bosentan, Boxi antineoplaston, Antipyrine, antisense oligonucleotides, apa dine, brefeldin, breflate, Brequinar Sodium, Bretazenil, doline, apafant, Apalcillin Sodium, apaxifylline, ApaZone, Bretylium Tosylate, Brifentanil Hydrochloride, brimoni aphidicolin glycinate, Apixifylline, Apomorphine Hydro dine, Brinolase, Brocresine, Brocrinat, Brofoxine, Broma chloride, apraclonidine, Apraclonidine Hydrochloride, doline Maleate, Bromazepam, Bromchlorenone, Brome Apramycin, Aprindine, Aprindine Hydrochloride, aproSulate lains, bromfenac, Brominidione, Bromocriptine, Sodium, Aprotinin, Aptazapine Maleate, aptiganel, apurinic Bromodiphenhydramine Hydrochloride, Bromoxanide, Bro acid, apurinic acid, aranidipine, Aranotin, Arbaprostil, mperidol, Bromperidol Decanoate, Brompheniramine Male arbekicin, arbidol, Hydrochloride, Arclofenin, ate, Broperamole, Bropirimine, Brotizolam, Bucainide Ardeparin Sodium, argatroban, Arginine, Argipressin Tan Maleate, bucindolol, Buclizine Hydrochloride, Bucromar nate, Arildone, aripiprazol, arotinolol, Arpinocid, Arteflene, one, BudeSonide, budipine, budotitane, Buformin, Bumet Artilide Fumarate, asimadoline, aspalatone, Asparaginase, anide, Bunaprolast, bunaZosin, Bunolol Hydrochloride, ASpartic Acid, ASpartocin, asperfuran, Aspirin, aspoxicillin, Bupicomide, Bupivacaine Hydrochloride, Buprenorphine Asprelin, Astemizole, Astromicin Sulfate, asulacrine, ata Hydrochloride, Bupropion Hydrochloride, Buramate, meStane, Atenolol, ateVirdine, Atipamezole, AtiproSin Male Buserelin Acetate, Buspirone Hydrochloride, BuSulfan, But ate, Atolide, Atorvastatin Calcium, Atosiban, Atovaquone, abarbital, Butacetin, Butaclamol Hydrochloride, Butalbital, atpenin B, Atracurium BeSylate, atrimustine, atrinositol, Butamben, Butamirate Citrate, Butaperazine, Butaprost, Atropine, Auranofin, aureobasidin A, Aurothioglucose, Butedronate Tetrasodium, butenafine, Buterizine, buthion Avilamycin, Avoparcin, Avridine, AXid, axinastatin 1, aXin ine Sulfoximine, Butikacin, Butilfenin, Butirosin Sulfate, astatin 2, axinastatin 3, AZabon, AZacitidinie, AZaclorzine Butixirate, butiXocort propionate, Butoconazole Nitrate, Hydrochloride, AZaconazole, azadirachtine, AZalanstat Butonate, Butopamine, Butoprozine Hydrochloride, Butor Dihydrochloride, AZaloxan Fumarate, AZanator Maleate, phanol, Butoxamine Hydrochloride, Butriptyline Hydro AZanidazole, AZaperone, AZaribine, AZaserine, azasetron, chloride, Cactinomycin, CadeXomer Iodine, Caffeine, cal AZatadine Maleate, AZathioprine, AZathioprine Sodium, anolide A, Calcifediol, Calcipotriene, calcipotriol, aZatoxin, azatyrosine, azelaic acid, azelastine, azelnidipine, Calcitonin, Calcitriol, Calcium Undecylenate, calphostin C, , AZetepa, azimilide, Azithromycin, AZlocillin, Calusterone, Cambendazole, camonagrel, camptothecin AZOlimine, AZOSemide, AZotomycin, Aztreonam, derivatives, canarypox IL-2, candesartan, Candicidin, can AZumolene Sodium, Bacampicillin Hydrochloride, baccatin doXatril, candoxatrilat, Caniglibose, Canrenoate Potassium, III, Bacitracin, Baclofen, bacoside A, bacoside B, bactobo Canrenone, capecitabine, Capobenate Sodium, Capobenic lamine, balanol, balaZipone, balhimycin, balofloxacin, bal Acid, Capreomycin Sulfate, capromab, capsaicin, Captopril, Salazide, Bambermycins, bambuterol, Bamethan Sulfate, Capuride, Caracemide, Carbachol, Carbadox, Carbam Bamifylline Hydrochloride, Bamnidazole, baohuoside 1, azepine, Carbamide Peroxide, Carbantel Lauryl Sulfate, Barmastine, barnidipine, Basifungin, Batanopride Hydro Carbaspirin Calcium, CarbaZeran, carbazomycin C, Carbe chloride, batebulast, Batelapine Maleate, Batimastat, beau nicillin Potassium, Carbenoxolone Sodium, Carbetimer, car vericin, Becanthone Hydrochloride, becaplermin, beclicona betocin, Carbidopa, Carbidopa-Levodopa, Carbinoxamine Zole, Beclomethasone Dipropionate, befloxatone, Maleate, Carbiphene Hydrochloride, Carbocloral, Car Beinserazide, Belfosdil, Belladonna, Beloxamide, bocysteine, Carbol-Fuchsin, Carboplatin, Carboprost, car BemeSetron, Bemitradine, Bemoradan, Benapry Zine Hydro bovir, carboxamide-amino-triaZO-le, carboxyamidotriazole, chloride, Benazepril Hydrochloride, Benazeprilat, Benda carboxymethylated beta-1,3-glucan, Carbuterol Hydrochlo calol Mesylate, Bendazac, Bendroflumethiazide, benflume ride, CaRest M3, Carfentanil Citrate, Carisoprodol, Carman tol, benidipine, Benorterone, Benoxaprofen, Benoxaprofen, tadine, Carmustine, CARN 700, Carnidazole, Caroxazone, Benoximate Hydrochloride, Benperidol, Bentazepam, Ben carperitide, Carphenazine Maleate, Carprofen, CarSatrin tiromide, Benurestat, Benzbromarone, Benzethonium Chlo Succinate, CartaZolate, carteolol, Carteolol Hydrochloride, ride, Benzetimide Hydrochloride, Benzilonium Bromide, cartilage derived inhibitor, Carubicin Hydrochloride, Caru BenZindopyrine Hydrochloride, benzisoxazole, Benzocaine, monam Sodium, carvedilol, carvotroline, Carvotroline benzochlorins, BenZoctamine Hydrochloride, BenZOdepa, Hydrochloride, carzelesin, casein kinase inhibitors (ICOS), benzoidaZOXan, BenZonatate, Benzoyl Peroxide, Ben castanospermine, caurumonam, cebaracetam, cecropin B, Zoylpas Calcium, benzoylstauroSporine, BenZquinamide, Cedefingol, Cefaclor, Cefadroxil, Cefamandole, Cefaparole, Benzthiazide, benztropine, Benztropine MeSylate, Benzy Cefatrizine, Cefazaflur Sodium, Cefazolin, Cefbuperazone, damine Hydrochloride, Benzylpenicilloyl Polylysine, bepri cefcapene pivoxil, cefdaloxime penteXil tosilate, Cefdinir, dil, Bepridil Hydrochloride, Beractant, Beraprost, Berefrine, cefditoren pivoxil, Cefepime, cefetamet, Cefetecol, berlafenone, bertosamil, Berythromycin, besipirdine, beta cefixime, cefluprenam, Cefnmenoxime Hydrochloride, alethine, betaclamycin B, Betamethasone, betamipron, Cefnmetazole, cefminlox, cefodizime, Cefonicid Sodium, betaxolol, Betaxolol Hydrochloride, Bethanechol Chloride, CefoperaZone Sodium, Ceforanide, cefoSelis, Cefotaxime Bethanidine Sulfate, betulinic acid, bevantolol, Bevantolol Sodium, Cefotetan, cefotiam, CefoXitin, cefoZopran, cefpi Hydrochloride, Bezafibrate, bFGF inhibitor, Bialamicol mizole, Cefpiramide, cefpirome, cefpodoxime proxetil, cef US 2006/OO18933 A1 Jan. 26, 2006 25 prozil, CefroXadine, cefSulodin, Ceftazidime, cefteram, cef Cyclizine, Cyclobendazole, cyclobenzaprine, cyclobut A, tibuten, Ceftizoxime Sodium, ceftriaxone, Cefuroxime, cyclobut G, cyclocapron, Cycloguanil Pamoate, Cyclohex celastrol, celikalim, celiprolol, cepacidine A, Cephacetrile imide, cyclopentanthraquinones, Cyclopenthiazide, Cyclo Sodium, Cephalexin, Cephaloglycin, Cephaloridine, Cepha pentolate Hydrochloride, Cyclophenazine Hydrochloride, lothin Sodium, Cephapirin Sodium, Cephradine, cer Cyclophosphamide, cycloplatam, Cyclopropane, CycloS iclamine, cerivastatin, Ceronapril, certoparin Sodium, Ceru erine, cycloSin, Cyclosporine, cyclothialidine, Cyclothiaz letide, Cetaben Sodium, Cetalkonium Chloride, Cetamolol ide, cyclothiazomycin, Cyheptamide, cypemycin, Cype Hydrochloride, cetiedil, cetirizine, Cetophenicol, Cetraxate namine Hydrochloride, Cyprazepam, Cyproheptadine Hydrochloride, cetrorelix, Cetylpyridinium Chloride, Hydrochloride, Cyprolidol Hydrochloride, cyproterone, Chenodiol, Chlophedianol Hydrochloride, , Cyproximide, CySteamine, Cysteine Hydrochloride, Cys Chlorambucil, Chloramphenicol, Chlordantoin, Chlordiaz tine, Cytarabine, Cytarabine Hydrochloride, cytarabine epoxide, Chlorhexidine Gluconate, chlorins, Chlormadinone ocfoSfate, cytochalasin B, cytolytic factor, cytostatin, Dac Acetate, chloroorienticin A, Chloroprocaine Hydrochloride, arbazine, dacliximab, dactimicin, Dactinomycin, daidzein, Chloropropamide, Chloroquine, chloroquinoxaline Sulfona Daledalin Tosylate, dalfopristin, Dalteparin Sodium, Dal mide, Chlorothiazide, Chlorotrianisene, Chloroxine, troban, Dalvastatin, danaparoid, Danazol, Dantrolene, Chloroxylenol, , Chlorphe daphlnodorin A, dapiprazole, dapitant, Dapoxetine Hydro niramine Maleate, Chlorpromazine, Chlorpropamide, Chlo chloride, DapSone, Daptomycin, DarglitaZone Sodium, rprothixene, Chlortetracycline Bisulfate, Chlorthalidone, darifenacin, darlucin A, Darodipine, darsidomine, Daunoru ChlorZoxazone, Cholestyramine Resin, Chromonar Hydro bicin Hydrochloride, Dazadrol Maleate, Dazepinil Hydro chloride, cibenzoline, cicaprost, Ciclafrine Hydrochloride, chloride, DaZmegrel, DaZopride Fumarate, DaZOXiben Ciclazindol, cicleSonide, cicletanine, CiclopiroX, Ciclopro Hydrochloride, Debrisoquin Sulfate, Decitabine, defer fen, cicloprolol, Cidofovir, Cidoxepin Hydrochloride, iprone, deflazacort, Dehydrocholic Acid, dehydrodidemnin Cifenline, CiglitaZone, Ciladopa Hydrochloride, cilansetron, B, Dehydroepiandrosterone, delapril, Delapril Hydrochlo Cilastatin Sodium, CilaZapril, cilnidipine, Cilobamine ride, Delavirdine MeSylate, deleguamine, delfaprazine, Del MeSylate, cilobradine, Cillofungin, ciloStaZol, Cimaterol, madinone Acetate, delmopinol, delphinidin, Demecarium Cimetidine, cimetropium bromide, Cinalukast, Cinanserin Bromide, Demeclocycline, Demecycline, Demoxepam, Hydrochloride, Cinepazet Maleate, Cinflumide, Cingestol, Denofungin, deoxypyridinoline, Depakote, deprodone, cinitapride, Cinnamedrine, Cinnarizine, cinolazepam, Cino Deprostil, depSidomycin, deramciclane, dermatan Sulfate, Xacin, Cinperene, Cinromide, CintaZone, Cintriamide, Ciot Desciclovir, Descinolone Acetonide, Desflurane, eronel, Cipamfylline, Ciprefadol Succinate, Ciprocinonide, Desipramine Hydrochloride, desirudin, Deslanoside, Ciprofibrate, Ciprofloxacin, ciprostene, Ciramadol, Cirole deslorelin, desmopressin, desogestrel, DeSonide, DeS mycin, cisapride, cisatracurium besilate, Cisconazole, Cis Oximetasone, desoxoamiodarone, DeSoxycorticosterone platin, cis-porphyrin, cistinexine, citalopram, Citenamide, Acetate, detajmium bit artrate, Deterenol Hydrochloride, citicoline, citreamicin alpha, cladribine, Clamoxyquin Detirelix Acetate, DevaZepide, Dexamethasone, Dexami Hydrochloride, Clarithromycin, clausenamide, Clavulanate Sole, Dexbrompheniramine Maleate, DeXchlorpheniramine Potassium, Clazolam, Clazolimine, clebopride, Clemastine, Maleate, Dexclamol Hydrochloride, Dexetimide, Dexfen Clentiazem Maleate, Clidinium Bromide, clinafloxacin, fluramine Hydrochloride, dexifosfamide, Deximafen, Dexi Clindamycin, Clioquinol, Clioxanide, Cliprofen, clobazam, vacaine, dexketoprofen, dexloxiglumide, DeXmedetomi Clobetasol Propionate, Clobetasone Butyrate, Clocortolone dine, DeXormaplatin, Dexoxadrol Hydrochloride, Acetate, Clodanolene, Clodazon Hydrochloride, clodronic Dexpanthenol, Dexpemedolac, Dexpropranolol Hydrochlo acid, Clofazimine, Clofibrate, Clofilium Phosphate, Cloge ride, DeXraZOxane, deXSotalol, dextrin 2-Sulphate, Dextro Stone Acetate, Clomacran Phosphate, Clomegestone amphetamine, Dextromethorphan, Dextrorphan Hydrochlo Acetate, Clometherone, clomethiazole, clomifene ana ride, Dextrothyroxine Sodium, deXVerapamil, DeZaguanine, logues, Clominorex, Clomiphene, Clomipramine Hydro dezinamide, deZOcine, Diacetolol Hydrochloride, chloride, Clonazepam, Clonidine, Clonitrate, Clonixeril, Diamocaine Cyclamate, Diapamide, Diatrizoate Meglu Clonixin, Clopamide, Clopenthixol, Cloperidone Hydro mine, Diatrizoic Acid, Diaveridine, Diazepam, Diaziquone, chloride, clopidogrel, Clopimozide, Clopipazan MeSylate, Diazoxide, Dibenzepin Hydrochloride, Dibenzothiophene, Clopirac, Cloprednol, Cloprostenol Sodium, CloraZepate Dibucaine, Dichliorvos, Dichloralphenazone, Dichlorphe Dipotassium, Clorethate, Clorexolone, Cloroperone Hydro namide, Dicirenone, Diclofenac Sodium, Dicloxacillin, dic chloride, Clorprenaline Hydrochloride, Clorsulon, Clorter ranin, Dicumarol, Dicyclomine Hydrochloride, Didanosine, mine Hydrochloride, CloSantel, Closiramine Aceturate, didemnin B, didox, Dienestrol, dienogest, Diethylcarbam Clothiapine, Clothixamide Maleate CloticaSone Propionate, azine Citrate, diethylhomospermine, diethylnorspermine, Clotrimazole, Cloxacillin BenZathine, Cloxyquin, CloZap Diethylpropion Hydrochloride, Diethylstilbestrol, Difenox ine, Cocaine, Coccidioidin, Codeine, Codoxime, Colchicine, imide Hydrochloride, Difenoxin, Diflorasone Diacetate, colestimide, Colestipol Hydrochloride, Colestolone, Col Difloxacin Hydrochloride, Difluanine Hydrochloride, Diflu forsin, Colfosceril Palmitate, Colistimethate Sodium, Colis cortolone, Diflumidone Sodium, Diflunisal, Difluprednate, tin Sulfate, collismycin A, collismycin B, Colterol Mesylate, Diftalone, Digitalis, Digitoxin, Digoxin, Dihexyverine combretastatin A4, combretastatin analogue, complestatin, Hydrochloride, dihydrexidine, dihydro-5-azacytidine, Dihy conagenin, Conorphone Hydrochloride, contignasterol, con drocodeine Bitartrate, Dihydroergotamine Mesylate, Dihy tortrostatin, Cormethasone Acetate, Corticorelin Ovine Tri droestosterone, Dihydrostreptomycin Sulfate, Dihydrotach flutate, Corticotropin, , CortivaZol, Corto ysterol, dihydrotaxol, 9-, Dilantin, Dilevalol Hydrochloride, doxone, coSalane, costatolide, CoSyntropin, cotinine, Diltiazem Hydrochloride, Dimefadane, Dimefline Hydro Coumadin, Coumermycin, crambescidin 816, Crilvastatin, chloride, Dimenhydrinate, Dimercaprol, Dimethadione, crisinatol, Cromitrile Sodium, Cromolyn Sodium, Crotami Dimethindene Maleate, Dimethisterone, dimethyl proStag ton, cryptophycin 8, cucumariosid, Cuprimyxin, curacin A, landin A1, Dimethyl Sulfoxide, dimethylhomospermine, curdlan Sulfate, curiosin, Cyclacillin, Cyclazocine, cycla dimiracetam, Dimoxamine Hydrochloride, Dinoprost, Dino Zosin, cyclic HPMPC, Cyclindole, Cycliramine Maleate, prostone, Dioxadrol Hydrochloride, dioxamycin, Diphenhy US 2006/OO18933 A1 Jan. 26, 2006 26 dramine Citrate, Diphenidol, Diphenoxylate Hydrochloride, Sate Sodium, ferristene, ferriXan, Ferrous Sulfate, Dried, diphenyl spiromustine, Dipivefin Hydrochloride, Dipivefrin, Ferumoxides, ferumoxsil, Fetoxylate Hydrochloride, fex dipliencyprone, diprafenone, dipropylnorspermine, Dipy ofenadine, FeZolamine Fumarate, Fiacitabine, Fialuridine, ridamole, Dipyrithione, Dipyrone, dirithromycin, discoder Fibrinogen 1125, filgrastim, Filipin, finasteride, Flavodilol mollide, Disobutamide, Disofenin, Disopyramide, Disoxaril, Maleate, flavopiridol, Flavoxate Hydrochloride, Flazalone, disulfiram, Ditekiren, Divalproex Sodium, Dizocilpine flecainide, flerobuterol, Fleroxacin, flesinoxan, Flestolol Maleate, Dobutamine, docarpamine, Docebenone, Doc Sulfate, Fletazepam, flezelastine, flobufen, Floctafenine, flo etaxel, Doconazole, docOSanol, dolfetilide, dolasetron, Ebas moxef, Flordipine, florfenicol, florifenine, flosatidil, Flose tine, ebiratide, ebrotidine, ebSelen, ecabapide, ecabet, eca quinan, Floxacillin, Floxuridine, fluiasterone, Fluazacort, dotril, ecdisteron, echicetin, echistatin, Echothiophate Flubanilate Hydrochloride, Flubendazole, Flucindole, Flu Iodide, Eclanamine Maleate, EclaZolast, ecomustine, Econa cloronide, Fluconazole, Flucytosine, Fludalanine, Fludara Zole, ecteinascidin 722, edaravone, Edatrexate, edelfosine, bine Phosphate, Fludazonium Chloride, Fludeoxyglucose F Edifolone Acetate, edobacomab, Edoxudine, edrecolomab, 18, Fludorex, Fludrocortisone Acetate, Flufenamic Acid, Edrophonium Chloride, edroxyprogesteone Acetate, efegat Flufenisal, Flumazenil, flumecinol, Flumequine, Flumeri ran, eflornithine, efonidipine, egualcen, Elantrine, eleatonin, done, Flumethasone, Flumetramide, FlumeZapine, Flumi elemene, eletriptan, elgodipine, eliprodil, Elsamitrucin, elte norex, Flumizole, Flumoxonide, flunarizine, Flunidazole, nae, Elucaine, emalkalim, emedastine, Emetine Hydrochlo Flunisolide, Flunitrazepam, Flunixin, fluocalcitriol, Fluoci ride, emiglitate, Emilium Tosylate, emitefur, emoctakin, nolone Acetonide, Fluocinonide, Fluocortin Butyl, Fluocor Enadoline Hydrochloride, enalapril, Enalaprilat, Enalkiren, tolone, Fluorescein, fluorodaunorunicin hydrochloride, enaZadrem, Encyprate, Endralazine MeSylate, EndrySone, Fluorodopa F 18, Fluorometholone, Fluorouracil, Flu Enflurane, englitaZone, Enilconazole, Enisoprost, Enlimo otracen Hydrochloride, Fluoxetine, Fluoxymesterone, flup mab, Enloplatin, Enofelast, Enolicam Sodium, Enoxacin, aroXan, Fluperamide, Fluperolone Acetate, Fluphenazine enoxacin, enoxaparin Sodium, Enoxaparin Sodium, Enoxi Decanoate, flupirtine, Fluprednisolone, FluproduaZone, Flu mone, Enpiroline Phosphate, Enprofylline, Enpromate, enta prostenol Sodium, FluguaZone, Fluradoline Hydrochloride, capone, enterostatin, Enviradene, EnviroXime, Ephedrine, Flurandrenolide, Flurazepam Hydrochloride, Flurbiprofen, Epicillin, Epimestrol, Epinephrine, Epinephryl Borate, Fluretofen, flurithromycin, Flurocitabine, Flurofamide, Epipropidine, Epirizole, epirubicin, Epitetracycline Hydro Flurogestone Acetate, Flurothyl, Fluroxene, Fluspiperone, chloride, Epithiazide, Epoetin Alfa, Epoetin Beta, EpoproS Fluspirilene, Fluticasone Propionate, flutrimazole, Flutro tenol, Epoprostenol Sodium, epoxymeXrenone, epristeride, line, fluvastatin, Fluvastatin Sodium, fluvoxamine, FluZina Eprosartan, eptastigmine, equilenin, Equilin, ErbuloZole, mide, Folic Acid, Follicle regulatory protein, Folliculostatin, erdosteine, Ergoloid MeSylates, Ergonovine Maleate, Fomepizole, Fonazine MeSylate, forasartan, forfenimex, for Ergotamine Tartrate, erSentilide, ErSofermin, erythritol, fenirmex, formeStane, Formocortal, formoterol, Fosarilate, Erythrityl Tetranitrate, Erythromycin, Esmolol Hydrochlo FoSazepam, Foscarnet Sodium, fosfomycin, Fosfonet ride, Esorubicin Hydrochloride, Esprocquin Hydrochloride, Sodium, foSinopril, Fosinoprilat, foSphenytoin, Fosquidone, Estazolam, Estradiol, Estramustine, estramustine analogue, Fostedil, fostriecin, fotemustine, Fuchsin, Basic, Fumoxicil EstraZinol Hydrobromide, Estriol, Estrofurate, estrogen ago lin, Fungimycin, Furaprofen, Furazolidone, Furazolium nists, estrogen antagonists, Estrogens, Conjugated, Estro Chloride, Furegrelate Sodium, Furobufen, Furodazole, gens, Esterified, Estrone, Estropipate, eSuprone, Etafedrine Furosemide, Fusidate Sodium, Fusidic Acid, gabapentin, Hydrochloride, Etanidazole, etanterol, Etarotene, EtaZolate Gadobenate Dimeglumine, gadobenic acid, gadobutrol, Hydrochloride, Eterobarb, ethacizin, Ethacrynate Sodium, Gadodiamide, gadolinium teXaphyrin, Gadopentetate Ethacrynic Acid, Ethambutol Hydrochloride, Ethamivan, Dimeglumine, gadoteric acid, Gadoteridol, Gadoverseta Ethanolamine Oleate, Ethehlorvynol, Ether, Ethinyl estra mide, galantamine, galdansetron, Galdansetron Hydrochlo diol, Ethiodized Oil, Ethionamide, Ethonam Nitrate, Etho ride, Gallamine Triethiodide, gallium nitrate, gallopamil, propazine Hydrochloride, EthosuXimide, Ethotoin, Ethoxa galocitabine, Gamfexine, gamolenic acid, Ganciclovir, Zene Hydrochloride, Ethybenztropine, Ethyl Chloride, Ethyl ganirelix, gelatinase inhibitors, Gemcadiol, Gemcitabine, Dibunate, Ethylestrenol, Ethyndiol, Ethynerone, Ethynodiol Gemeprost, Gemfibrozil, Gentamicin Sulfate, Gentian Vio Diacetate, Etibendazole, Etidocaine, Etidronate Disodium, let, gepirone, Gestaclone, Gestodene, GeStonorone Etidronic Acid, Etifenin, Etintidine Hydrochloride, eti Caproate, Gestrinone, GeVotroline Hydrochloride, giriso Zolam, Etodolac, Etofenamate, Etoformin Hydrochloride, pam, glaspimod, glaucocalyxin A, Glemanserin, Gliamilide, Etomidate, EtonogeStrel, Etoperidone Hydrochloride, Eto , Glicetanile Sodium, Gliflumide, Glimepiride, poside, Etoprine, Etoxadrol Hydrochloride, EtoZolin, etra Glipizide, Gloximonam, Glucagon, glutapyrone, glutathione bamine, Etretinate, Etryptamine Acetate, Eucatropine inhibitors, Glutethimide, Glyburide, glycopine, glycopril, Hydrochloride, Eugenol, Euprocin Hydrochloride, eveni Glycopyrrolate, Glyhexamide, Glymidine Sodium, Glyoc nomicin, Exametazime, examorelin, Exaprolol Hydrochlo tamide, Glyparamide, Gold Au 198, Gonadoctrinins, Gona ride, exemestane, fadrozole, faerieflungin, Famciclovir, dorelin, Gonadotropins, Goserelin, Gramicidin, Granisetron, Famotidine, Fampridine, fantofarone, Fantridone Hydro grepafloxacin, Griseofulvin, Guaiapate, Guaithylline, Gua chloride, faropenem, fasidotril, fasudil, faZarabine, fedot nabenz, Guanabenz, Acetate, Guanadrel Sulfate, Guancy Ozine, felbamate, Felbinac, Felodipine, Fely pressin, Fenala dine, Guanethidine Monosulfate, Guanfacine Hydrochlo mide, Fenamole, Fenbendazole, Fenbufen, Fencibutirol, ride, Guanisoquin Sulfate, Guanoclor Sulfate, Guanoctine Fenclofenac, Fenclonine, Fenclorac, Fendosal, FeneStrel, Hydrochloride, GuanoXabenz, Guanoxan Sulfate, Guanoxy Fenethylline Hydrochloride, Fenfluramine Hydrochloride, fen Sulfate, Gusperimus Trihydrochloride, Halazepam, Hal Fengabine, Fenimide, Fenisorex, Fenmetozole Hydrochlo cinonide, halichondrin B, Halobetasol Propionate, halofan ride, Fenmetramide, Fenobam, Fenoctimine Sulfate, fenofi trine, Halofantrine Hydrochloride, Halofenate, brate, fenoldopam, Fenoprofen, Fenoterol, Fenpipalone, Halofuginone Hydrobromide, halomon, Halopemide, Halo Fenprinast Hydrochloride, FenproStalene, Fenguizone, fen peridol, halopredone, Haloprogesterone, Haloprogin, Hal retinide, fenspiride, Fentanyl Citrate, Fentiazac, Fenticlor, othane, Halquinols, Hamycin, Han memopausal gonadotro fenticonazole, Fenyripol Hydrochloride, fepradinol, ferpifo pins, hatomamicin, hatomarubigin A, hatomarubigin B, US 2006/OO18933 A1 Jan. 26, 2006 27 hatomarubigin C, hatomarubigin D, Heparin Sodium, hep ipine, lacidipine, lactitol, lactivicin, laennec, lafutidine, Sulfam, heregulin, Hetacillin, Heteronium Bromide, lamellarin-N triacetate, lamifiban, Lamivudine, Lamot Hexachlorophene:Hydrogen Peroxide, Hexafluorenium rigine, lanoconazole, Lanoxin, lanperisone, lanreotide, Lan Bromide, hexamethylene bisacetamide, Hexedine, Hex Soprazole, latanoprost, lateritin, laurocapram, Lauryl Iso obendine, Hexoprenaline Sulfate, Hexylresorcinol, Hista quinolinium Bromide, LaVoltidine Succinate, lazabemide, mine Phosphate, Histidine, Histoplasmin, Histrelin, Homa Lecimibide, leinamycin, lemildipine, leminoprazole, lener tropine Hydrobromide, Hoquizil Hydrochloride, Human cept, Leniquinsin, lenograstim, Lenperone, lentinan Sulfate, chorionic gonadotropin, Hycanthone, Hydralazine Hydro leptin, leptolstatin, lercanidipine, Lergotrile, lerisetron, chloride, Hydralazine Polistirex, Hydrochlorothiazide, Letimide Hydrochloride, letraZuril, letrozole, Leucine, leu Hydrocodone Bitartrate, Hydrocortisone, Hydroflumethiaz comyzin, Leuprolide Acetate, leuprolide--estrogen-proges ide, Hydromorphone Hydrochloride, Hydroxyamphetamine terone, leuprorelin, Levamfetamine Succinate, levamisole, Hydrobromide, Hydroxychloroquine Sulfate, Hydroxyphe Levdobutamine Lactobionate, Leveromakalim, levetirac namate, Hydroxyprogesterone Caproate, Hydroxyurca, etam, Levey closerine, leVobetaxolol, levobunolol, levobupi Hydroxyzine Hydrochloride, Hymecromone, Hyoscyamine, vacaine, levocabastine, levocarnitine, Levodopa, levodro hypericin, Ibafloxacin, ibandronic acid, ibogaine, Ibopam propizine, levofloxacin, Levofuraltadone, Levoleucovorin ine, ibudilast, Ibufenac, Ibuprofen, Ibutilide Fumarate, Icati Calcium, Levomethadyl Acetate, Levomethadyl Acetate bant Acetate, Ichthammol, Icotidine, idarubicin, idoxifene, Hydrochloride, levomoprolol, Levonantradol Hydrochlo Idoxuridine, idramantone, Iemefloxacin, IeSopitron, ride, Levonordefrin, Levonorgestrel, Levopropoxyphene Ifetroban, Ifosfamide, Ilepeimide, illimaquinone, ilmofoS NapSylate, Levopropylcillin Potassium, leVormeloxifene, ine, ilomastat, Ilonidap, illoperidone, iloprost, Imafen Hydro Levorphanol Tartrate, levosimendan, levOSulpiride, chloride, ImaZodan Hydrochloride, imidapril, imidazenil, Levothyroxine Sodium, Levoxadrol Hydrochloride, Lexi imidazoacridones, Imidecyl Iodine, Imidocarb Hydrochlo pafant, Lexithromycin, liarozole, Libenzapril, Lidamidine ride, Imidoline Hydrochloride, Imidurea, Imiloxan Hydro Hydrochloride, Lidocaine, Lidofenin, Lidoflazine, Lifariz chloride, Imipenem, Imipramine Hydrochloride, imiqui ine, Lifibrate, Lifibrol, Linarotene, Lincomycin, linear mod, immunostimulant peptides, Impromidine polyamine analogue, Linogliride, Linopirdine, linotroban, Hydrochloride, Indacrinone, Indapamide, Indecainide linsidomine, lintitript, lintopride, Liothyronine I 125, liothy Hydrochloride, Indeloxazine Hydrochloride, Indigotindisul ronine Sodium, Liotrix, lirexapride, lisinopril, lisSoclinamide fonate Sodium, indinavir, Indocyanine Green, Indolapril 7, Lixazinone Sulfate, lobaplatin, Lobenzarit Sodium, Lobu Hydrochloride, Indolidan, indometacin, Indomethacin cavir, Lodelaben, lodoxamide, Lofemizole Hydrochloride, Sodium, Indoprofen, indoramin, Indorenate Hydrochloride, Lofentanil Oxalate, Lofepramine Hydrochloride, Lofexidine Indoxole, Indriline Hydrochloride, inocoterone, inogatran, Hydrochloride, lombricine, Lomefloxacin, lomerizine, inolimomab, InoSitol Niacinate, Insulin, interferons, inter Lometraline Hydrochloride, lometrexol, Lomofungin, leukins, Intrazole, Intriptyline Hydrochloride, iobenguane, Lomoxicam, Lomustine, Lonapalene, lonazolac, Iobenzamic Acid, iobitridol, Iocarmate Meglumine, Iocar lonidamine, Loperamide Hydrochloride, loracarbef, mic Acid, Iocetamic Acid, Iodamide, Iodine, Iodipamide Lorajmine Hydrochloride, loratadine, Lorazepam, Lorbam Meglumine, Iodixanol, iodoamiloride, Iodoantipyrine I 131, ate, Lorcainide Hydrochloride, LorecleZole, Loreinadol, lor Iodocholesterol I 131, iododoxorubicin, Iodohippurate glumide, Lormetazepam, Lornoxicam, lornoxicam, Lorta Sodium I 131, Iodopyracet I 125, Iodoquinol, Iodoxamate lamine, LorZafone, losartan, losigamone, loSOXantrone, Meglumine, Iodoxamie Acid, Ioglicic Acid, Iofetamine LOSulazine Hydrochloride, loteprednol, lovastatin, loviride, Hydrochloride I 123, iofratol, Ioglucol, Ioglucomide, Iogly Loxapine, Loxoribine, lubeluzole, Lucanthone Hydrochlo camic Acid, Iogulamide, Iohexol, iomeprol, Iomethin I 125, ride, Lufironil, Lurosetron MeSylate, lurtotecan, luteinizing Iopamidol, Iopanoic Acid, iopentol, Iophendylate, Ioproce hormone, lutetium, Lutrelin Acetate, luZindole, Lyapolate mic Acid, iopromide, Iopronic Acid, Iopydol, Iopy done, Sodium, Lycetamine, lydicamycin, Lydimycin, Lynestrenol, iopyrol, Iosefamic Acid, IoSeric Acid, IoSulamide Meglu Lypressin, Lysine, lySofylline, lysostaphin, lytic peptides, mine, IoSumetic Acid, IotaSul, Iotetric Acid, Iothalamate Maduramicin, Mafenide, magainin 2 amide, Magnesium Sodium, Iothalamic Acid, iotriside, Iotrolan, IotroXic Acid, Salicylate, Magnesium Sulfate, magnolol, maitansine, Male Iotyrosine 1 131, IoverSol, Ioxagiate Sodium, Ioxaglate thamer, mallotochromene, mallotojaponin, Malotilate, Meglumine, Ioxaglic Acid, ioxilan, Ioxotrizoic Acid, ipazil malotilate, mangafodipir, manidipine, maniwamycin A, ide, ipenoxazone, ipidacrine, Ipodate Calcium, ipomeanol, Mannitol, mannostatin A, manumycin E, manumycin F, 4-, pratropium Bromide, ipriflavone, Iprindole, Iprofenin, mapinastine, Maprotiline, marimastat, Martek 8708, Martek Ipronidazole, I proplatin, Iproxamine Hydrochloride, ipsa 92211, Masoprocol, maspin, massetolide, matrilysin inhibi pirone, irbesartan, irinotecan, irloxacin, iroplact, irSoglad tors, Maytansine, Mazapertine Succiniate, Mazindol, ine, Irtemazole, isalsteine, Isamoxole, isbogrel, Isepamicin, Mebendazole, Mebeverine Hydrochloride, Mebrofenin, isobengaZole, Isobutamben, ISOcarboxazid, ISOconazole, Mebutamate, Mecamylamine Hydrochloride, Mechlore Isoetharine, isofloxythepin, Isoflupredone Acetate, Isoflu thamine Hydrochloride, Meclocycline, Meclofenamate rane, Isoflurophate, isohomohalicondrin B, Isoleucine, Iso Sodium, Mecloqualone, Meclorisone Dibutyrate, mazole Hydrochloride, Isomylamine Hydrochloride, Iso Medazepam Hydrochloride, Medorinone, Medrogestone, niazid, Isopropamide Iodide, Isopropyl Alcohol, isopropyl Medroxalol, Medroxyprogesterone, Medrysone, Meelizine unoprostone, Isoproterenol Hydrochloride, ISOSorbide, ISOS Hydrochloride, Mefenamic Acid, Mefenidil, Mefenorex orbide Mononitrate, Isotiquimide, Isotretinoin, ISOXepac, Hydrochloride, Mefexamide, Mefloquine Hydrochloride, ISOXicam, ISOXSuprine Hydrochloride, isradipine, itameline, Mefruside, Megalomicin Potassium Phosphate, Megestrol itasetron, ItaZigrel, itopride, Itraconazole, Ivermectin, jas Acetate, Meglumine, Meglutol, , Meli plakinolide, Josamycin, kahalalide F, Kalafungin, Kanamy tracen Hydrochloride, Melphalan, Memotine Hydrochlo cin Sulfate, Ketamine Hydrochloride, Ketanserin, KetaZO ride, Menabitan Hydrochloride, Menoctone, menogaril, cine, Ketazolam, Kethoxal, Ketipramine Fumarate, Menotropins, Meobentine Sulfate, Mepartricin, Mepen Ketoconazole, Ketoprofen, Ketorfanol, ketorolac, Ketotifen Zolate Bromide, Meperidine Hydrochloride, Mephentermine Fumarate, Kitasamycin, Labetalol Hydrochloride, Lacid Sulfate, Mephenytoin, Mephobarbital, Mepivacaine Hydro US 2006/OO18933 A1 Jan. 26, 2006 28 chloride, Meprobamate, Meptazinol Hydrochloride, Mequi hazoline Hydrochloride, naphterpin, Naproxen, NaproXol, dox, Meralein Sodium, merbarone, Mercaptopurine, Mer napsagatran, Naranol Hydrochloride, Narasin, naratriptan, cufenol Chloride, Mercury, Ammoniated, Merisoprol Hg nartograstim, nasaruplase, Natamycin, nateplase, Nax 197, Meropenem, Mesalamine, Meseclazone, Mesoridazine, agolide Hydrochloride, Nebivolol, Nebramycin, nedaplatin, Mesterolone, Mestranol, Mesuprine Hydrochloride, Metalol Nedocromil, Nefazodone Hydrochloride, Neflumozide Hydrochloride, Metaproterenol Polistirex, Metaraminol Hydrochloride, Nefopam Hydrochloride, NeleZaprine Male Bitartrate, Metaxalone, Meteneprost, meterelin, Metformin, ate, Nemazoline Hydrochloride, nemorubicin, Neomycin Methacholine Chloride, Methacycline, Methadone Hydro Palmitate, Neostigmine Bromide, neridronic acid, Netilmi chloride, Methadyl Acetate, Methalthiazide, Methamphet cin Sulfate, neutral endopeptidase, Neutramycin, Nevirap amine Hydrochloride, Methaqualone, Methazolamide, ine, Nexeridine Hydrochloride, Niacin, Nibroxane, Nicar Methdilazine, Methenamine, Methenolone Acetate, Meth dipine Hydrochloride, Nicergoline, Niclosamide, etoin, Methicillin Sodium, Methimazole, methioninase, Nicorandil, Nicotinyl Alcohol, Nifedipine, Nifirmerone, Methionine, Methisazone, Methixene Hydrochloride, Nifluridide, Nifuradene, Nifuraldezone, Nifuratel, Nifura Methocarbamol, Methohexital Sodium, Methopholine, trone, Nifurdazil, Nifurimide, Nifurpirinol, Nifurcquinazol, Methotrexate, Methotrimeprazine, methoxatone, Methoxy Nifurthiazole, nilutamide, Nilvadipine, Nimazone, Nimo flurane, Methsuximide, Methyclothiazide, Methyl Palmox dipine, niperotidine, niravoline, Niridazole, nisamycin, Nis irate, Methylatropine Nitrate, Methylbenzethonium Chlo buterol Mesylate, nisin, Nisobamate, Nisoldipine, Nisoxet ride, Methyldopa, Methyldopate Hydrochloride, Methylene ine, Nisterime Acetate, NitarSone, nitaZOXanide, nitecapone, Blue, Methylergonovine Maleate, methylhistamine, R-al Nitrafudam Hydrochloride, Nitralamine Hydrochloride, Nit pha, methylinosine monophosphate, Methylphenidate ramisole Hydrochloride, Nitrazepam, Nitrendipine, Nitrocy Hydrochloride, Methylprednisolone, Methyltestosterone, cline, Nitrodan, Nitrofurantoin, Nitrofurazone, Nitroglyc Methynodiol Diacelate, Methysergide, Methysergide Male erin, Nitromersol, Nitromide, Nitromifene Citrate, Nitrous ate, Metiamide, Metiapine, Metioprim, metipamide, Oxide, nitroxide antioxidant, nitrullyn, Nivazol, Nivine Metipranolol, Metizoline Hydrochloride, Metkephamid done Sodium, Nizatidine, Noberastine, Nocodazole, Acetate, metoclopramide, Metocurine Iodide, Metogest, Nogalamycin, Nolinium Bromide, Nomifensine Maleate, Metolazone, Metopimazine, Metoprine, Metoprolol, Meto Noracymethadol Hydrochloride, Norbolethone, Norepi quizine, metrifonate, Metrizamide, Metrizoate Sodium, nephrine Bitaritrate, Norethindrone, Norethynodrel, Nor Metronidazole, Meturedepa, Metyrapone, Metyrosine, floxacin, Norflurane, Norgestimate, Norgestomet, Norg Mexiletine Hydrochloride, Mexrenoate Potassium, estrel, Nortriptyline Hydrochloride, NoScapine, Novobiocin Mezlocillin, mfonelic Acid, Mianserin Hydrochloride, Sodium, N-Substituted benzaimides, NufenoXole, mibefradil, Mibefradil Dihydrochloridc, Mibolerone, mich Nylestriol, Nystatin, O6-benzylguanine, Obidoxime Chlo ellamine B, Miconazole, microcolin A, Midaflur, Mida ride, Ocaperidone, Ocfentanil Hydrochloride, Ocinaplon, Zolam Hydrochloride, midodrine, mifepristone, Mifobate, Octanoic Acid, Octazamide, Octenidine Hydrochloride, miglitol, millacemide, milameline, mildronate, Milenperone, Octodrine, Octreotide, Octriptyline Phosphate, Ofloxacin, Milipertine, milnacipran, Milrinone, miltefosine, Mimbane Ofornine, okicenone, Olanzapine, oligonucleotides, olopata Hydrochloride, minaprine, Minaxolone, Minocromil, dine, olprinone, olSalazine, Olsalazine Sodium, Olvanil, Minocycline, Minoxidil, Mioflazine Hydrochloride, mioka omeprazole, onapristone, Ondansetron, Ontazolast, Oocyte mycin, mipragoside, mirfentanil, mirimoStim, Mirincamy maturation inhibitor, Opipramol Hydrochloride, oracin, cin Hydrochloride, Mirisetron Maleate, Mirtazapine, mis Orconazole Nitrate, Orgotein, Orlislat, Ormaplatin, Orme matched double stranded RNA, Misonidazole, Misoprostol, toprim, Ornidazole, Orpanoxin, Orphenadrine Citrate, Mitindomide, Mitocarcin, Mitocromin, Mitogillin, mitogua OSaterone, otenZepad, Oxacillin Sodium, OXagrelate, Oxali Zone, mitolactol, Mitomalcin, Mitomycin, mitonafide, Mito platin, OXamarin Hydrochloride, oxamisole, Oxamniquine, Sper, Mitotane, mitoxantrone, mivacurium chloride, mivaZ oxandrolone, Oxantel Pamoate, Oxaprotiline Hydrochlo erol, mixanpril, Mixidine, mizolastine, mizoribine, ride, Oxaprozin, OXarbazole, Oxatomide, oxaunomycin, Moclobemide, modafinil, Modaline Sulfate, Modecainide, Oxazepam, Oxcarbazepine, Oxendolone, Oxethazaine, moexipril, mofarotene, Mofegiline Hydrochloride, mof Oxetorone Fumarate, Oxfendazole, Oxfenicine, Oxibenda eZolac, molgramoStim, MolinaZone, Molindone Hydrochlo Zole, oxiconazole, Oxidopamine, Oxidronic Acid, OXifungin ride, Molsidomine, mometasone, Monatepil Maleate, Mon Hydrochloride, Oxilorphan, Oximonam, Oximonam ensin, Monoctanoin, Montelukast Sodium, montirelin, Sodium, OXiperomide, OXiracetam, OXiramide, Oxisuran, mopidamol, moracizine, Morantel Tartrate, Moricizine, Oximetidine Hydrochloride, oxodipine, Oxogestone Phen Morniflumate, Morphine Sulfate, Morrhuate Sodium, propionate, Oxolinic Acid, Oxprenolol Hydrochloride, Oxt mosapramine, mosapride, motilide, Motretinide, Moxalac riphylline, Oxybutynin Chloride, Oxychlorosene, Oxyc tam Disodium, Moxazocine, moxiraprine, Moxinidazole, odone, Oxymetazoline Hydrochloride, Oxymetholone, moxonidine, Mumps Skin Test Antigen, mustard anticancer Oxymorphone Hydrochloride, Oxypertine, Oxyphenbuta agent, Muzolimine, mycaperoxide B, Mycophenolic Acid, Zone, Oxypurinol, Oxytetracycline, Oxytocin, OZagrel, OZo myriaporone, Nabazenil, Nabilone, Nabitan Hydrochloride, linone, Paclitaxel, palauamine, Paldimycin, palinavir, palmi Naboctate Hydrochloride, Nabumetone, N-acetyldinaline, toylrhizoxin, Palmoxirate Sodium, pamaqueside, Pamatolol Nadide, nadifloxacin, Nadolol, nadroparin calcium, nafadot Sulfate, pamicogrel, Pamidronate Disodium, pamidronic ride, nafamoStat, nafarelin, Nafcillin Sodium, Nafenopin, acid, Panadiplon, panamesine, panaxytriol, Pancopride, Nafimidone Hydrochloride, Naflocort, Nafomine Malate, Pancuronium Bromide, panipenem, pannorin, panomifene, Nafoxidine Hydrochloride, Nafronyl Oxalate, Naftifine pantethine, pantoprazole, Papaverine Hydrochloride, para Hydrochloride, naftopidil, naglivan, nagreStip, Nalbuphine bactin, Parachlorophenol, Paraldehyde, Paramethasone Hydrochloride, Nalidixate Sodium, Nalidixic Acid, Acetate, Paranyline Hydrochloride, Parapenzolate Bromide, nalmefene, NalmeXOne Hydrochloride, naloxone-pentaZO Pararosaniline Pamoate, Parbendazole, Parconazole Hydro cine, Naltrexone, NamoXyrate, Nandrolone Phenpropionate, chloride, Paregoric, Pareptide Sulfate, Pargyline Hydrochlo Nantradol Hydrochloride, Napacitadine Hydrochloride, ride, parnaparin Sodium, Paromomycin Sulfate, Paroxetine, napadisilate, Napamezole Hydrochloride, napavin, Nap parthenolide, Partricin, Paulomycin, paZelliptine, PaZina US 2006/OO18933 A1 Jan. 26, 2006 29 clone, PaZOxide, paZufloxacin, pefloxacin, pegaspargase, caterol Hydrochloride, Prochlorperazine, Procinonide, Pro Pegorgotein, Pelanserin Hydrochloride, peldesine, Peliomy clonol, Procyclidine Hydrochloride, Prodilidine Hydrochlo cin, Pelretin, Pelrinone Hydrochloride, Pemedolac, Pemerid ride, Prodolic Acid, Profadol Hydrochloride, Progabide, Nitrate, pemirolast, Pemoline, Penamecillin, Penbutolol Sul Progesterone, Proglumide, Proinsulin Human, Proline, Pro fate, Penciclovir, Penfluridol, Penicillin G BenZathine, Peni lintane Hydrochloride, Promazine Hydrochloride, Promet cillin G Potassium, Penicillin G Procaine, Penicillin G hazine Hydrochloride, Propafenone Hydrochloride, Sodium, Penicillin V, Penicillin V BenZathine, Penicillin V propagermanium, Propanidid, Propantheline Bromide, Pro Hydrabamine, Penicillin V Potassium, Pentabamate, Pen paracaine Hydrochloride, Propatyl Nitrate, propentofylline, taerythritol Tetranitrate, pentafuside, pentamidine, pentam Propenzolate Hydrochloride, Propikacin, Propiomazine, orphone, Pentamustine, Pentapiperium Methylsulfate, Pen Propionic Acid, propionylcarnitine, L-, propiram, propiram-- tazocine, Pentetic Acid, Pentiapine Maleate, pentigetide, paracetamol, propiverine, Propofol, Propoxycaine Hydro Pentisomicin, Pentizidone Sodium, Pentobarbital, Pento chloride, Propoxyphene Hydrochloride, Propranolol Hydro mone, Pentopril, pentosan, pentostatin, Pentoxifylline, Pen chloride, Propulsid, propyl bis-acridone, Propylhexedrine, trinitrol, pentrozole, Peplomycin Sulfate, Pepstatin, perflu Propyliodone, Propylthiouracil, ProquaZone, Prorenoate bron, perfofamide, Perfosfamide, pergolide, Perhexiline Potassium, Proroxan Hydrochloride, Proscillaridin, Prostal Maleate, perillyl alcohol, Perindopril, perindoprilat, Perlap ene, prostratin, Protamine Sulfate, protegrin, Protirelin, pro ine, Permethrin, peroSpirone, Perphenazine, Phenacemide, toSufloxacin, Protriptyline Hydrochloride, Proxazole, ProX phenaridine, phenazinomycin, Phenazopyridine Hydrochlo azole Citrate, ProXicromil, Proxorphan Tartrate, ride, Phenbutazone Sodium Glycerate, Phencarbamide, prulifloxacin, Pseudoephedrine Hydrochloride, Puromycin, Phencyclidine Hydrochloride, Phendimetrazine Tartrate, purpurins, Pyrabrom, Pyrantel Pamoate, Pyrazinamide, Phenelzine Sulfate, Phenmetrazine Hydrochloride, Phe Pyrazofurin, pyrazoloacridine, PyridoStigmine Bromide, nobarbital, Phenoxybenzamine Hydrochloride, Phenprocou Pyrilamine Maleate, Pyrimethamine, Pyrinoline, Pyrithione mon, phenserine, phensuccinal, PhenSuximide, Phenter Sodium, Pyrithione Zinc, Pyrovalerone Hydrochloride, mine, Phentermine Hydrochloride, phentolamine mesilate, Pyroxamine Maleate, Pyrrocaine, Pyrroliphene Hydrochlo Phentoxifylline, Phenyl Aminosalicylate, phenylacetate, ride, Pyrrolnitrin, Pyrvinium Pamoate, Quadazocine Mesy Phenylalanine, phenylalanylketoconazole, PhenylbutaZone, late, Quazepam, Quazinone, QuaZodine, QuaZolast, quetiap Phenylephrine Hydrochloride, Phenylpropanolamine ine, quiflapon, quinagolide, Quinaldine Blue, quinapril, Hydrochloride, Phenylpropanolamine Polistirex, Phenyra Quinaprilat, QuinaZOsin Hydrochloride, Quinbolone, Quinc midol Hydrochloride, Phenytoin, phosphatase inhibitors, tolate, Quindecamine Acetate, Quindonium Bromide, Physostigmine, picenadol, picibanil, Picotrin Diolamine, Quinelorane Hydrochloride, Quinestrol, Quinfamide, picroliv, picumeterol, pidotimod, Pifarnine, Pilocarpine, pil , Quingestrone, Quinidine Gluconate, Sicainide, pimagedine, Pimetine Hydrochloride, pimilprost, Quinielorane Hydrochloride, Quinine Sulfate, Quinpirole Pimobendan, Pimozide, Pinacidil, Pinadoline, Pindolol, pin Hydrochloride, Quinterenol Sulfate, Quinuclium Bromide, nenol, pinocebrin, Pinoxepin Hydrochloride, pioglitaZone, Quinupristin, Maleate, Rabeprazole Sodium, Pipamperone, Pipazethate, pipecuronium bromide, Piperac Racephenicol, Racepinephrine, raf antagonists, Rafoxanide, etazine, Piperacillin Sodium, Piperamide Maleate, Pipera Ralitoline, raloxifene, raltitrexed, ramatroban, Ramipril, zine, Pipobroman, Piposulfan, Pipotiazine Palmitate, Ramoplanin, ramosetron, ranelic acid, Ranimycin, Raniti Pipoxolan Hydrochloride, Piprozolin, Piquindone Hydro dine, ranolazine, Rauwolfia Serpentina, recainam, Recainam chloride, Piquizil Hydrochloride, Piracetam, Pirandamine Hydrochloride, Reclazepam, regaVirumab, RegramoStim, Hydrochloride, pirarubicin, Pirazmonam Sodium, Pirazolac, Relaxin, Relomycin, Remacemide Hydrochloride, Remifen Pirbenicillin Sodium, Pirbuterol Acetate, Pirenperone, tanil Hydrochloride, Remiprostol, Remoxipride, Repirinast, Pirenzepine Hydrochloride, piretanide, Pirfenidone, Piridi Repromicin, Reproterol Hydrochloride, Reserpine, resin cillin Sodium, Piridironate Sodium, Piriprost, piritrexim, feratoxin, Resorcinol, retelliptine demethylated, reticulon, Pirlimycin Hydrochloride, pirlindole, pirmagrel, Pirmenol reviparin Sodium, revizinone, rhenium Re 186 etidronate, Hydrochloride, Pirnabine, Piroctone, Pirodavir, pirodomast, rhizoxin, Ribaminol, Ribavirin, Riboprine, ribozymes, Pirogliride Tartrate, Pirolate, Pirolazamide, Piroxantrone ricasetron, Ridogrel, Rifabutin, Rifametane, Rifamexil, Hydrochloride, Piroxicam, Piroximone, Pirprofen, Pirquino Rifamide, Rifampin, Rifapentine, Rifaximin, RII retina Zol, Pirsidomine, Prenylamine, Pituitary, Posterior, Pivampi mide, rilopiroX, Riluzole, rimantadine, RimcaZOle Hydro cillin Hydrochloride, Pivopril, Pizotyline, placetin A, plati chloride, Rimexolone, Rimiterol Hydrobromide, rimopro num compounds, platinum-triamine complex, Plicamycin, gin, riodipine, Rioprostil, Ripazepam, ripisartan, Plomestane, Pobilukast Edamine, Podofilox, Poisonoak Risedronate Sodium, risedronic acid, Risocaine, Risotilide Extract, Poldine Methylsulfate, Poliglusam, Polignate Hydrochloride, rispenzepine, Risperdal, Risperidone, Sodium, Polymyxin B Sulfate, Polythiazide, Ponalrestat, Ritanserin, ritipenem, Ritodrine, Ritolukast, ritonavir, riza Porfimer Sodium, Porfiromycin, Potassium Chloride, Potas triptan benzoate, Rocastine Hydrochloride, Rocuronium sium Iodide, Potassium Permanganate, PoVidone-Iodine, Bromide, Rodocaine, Roflurane, Rogletimide, rohitukine, Practolol, Pralidoxime Chloride, Pramiracetam Hydrochlo rokitamycin, Roletamicide, Rolgamidine, Rolicyprine, ride, Pramoxine Hydrochloride, Pranolium Chloride, Prava Rolipram, Rolitetracycline, Rolodine, RomaZarit, romurtide, doline Maleate, Pravastatin (Pravachol), Prazepam, Pra Ronidazole, ropinirole, Ropitoin Hydrochloride, ropiv Zosin, Prazosin Hydrochloride, Prednazate, Prednicarbate, acaine, Ropizine, roquinimex, Rosaramicin, ROSoxacin, Prednimustine, Prednisolone, Prednisone, Prednival, Preg Rotoxamine, roXaitidine, RoxarSone, roXindole, roXithromy menolone Succiniate, Prenalterol Hydrochloride, Pridefine cin, rubiginone B1, ruboxyl, rufloxacin, rupatidine, Ruta Hydrochloride, Prifelone, Prilocaine Hydrochloride, mycin, ruzadolane, Sabeluzole, Safingol, Safironil, Saintopin, Prilosec, Primacquine Phosphate, Primidolol, Primidone, salbutamol, R-, Salcolex, Salethamide Maleate, Salicyl Prinivil, Prinomide Tromethamine, PrinoXodan, Prizidilol Alcohol, Salicylamide, Salicylate Meglumine, Salicylic Hydrochloride, Proadifen Hydrochloride, Probenecid, Pro Acid, Salmeterol, Salnacedin, Salsalate, Sameridine, Sam bicromil Calcium, Probucol, Procainamide Hydrochloride, patrilat, Sancycline, Sanfetrinem, Sanguinarium Chloride, Procaine Hydrochloride, Procarbazine Hydrochloride, Pro Saperconazole, Saprisartan, Sapropterin, Saquinavir, Sara US 2006/OO18933 A1 Jan. 26, 2006 30 floxacin Hydrochloride, Saralasin Acetate, SarCNU, sarco Hydrochloride, Teludipine Hydrochloride, Temafloxacin phytol A, SargramoStim, Sarmoxicillin, Sarpicillin, Sar Hydrochloride, Tematropium Methyl sulfate, Temazepam, pogrelate, Saruplase, Saterinone, Satigrel, Satumomab Temelastine, temocapril, Temocillin, temoporfin, temozolo pendetide, Schick Test Control, Scopafungin, Scopolamine mide, Tenidap, Teniposide, tenosal, tenoxicam, tepirindole, Hydrobromide, Scrazaipine Hydrochloride, Sdi 1 mimetics, Tepoxalin, Teprotide, teraZOsin, Terbinafine, Terbutaline Secalciferol, Secobarbital, Seelzone, Seglitide Acetate, Sel Sulfate, Terconazole, terfenadine, terflavoxate, terguride, egiline, Selegiline Hydrochloride, Selenium Sulfide, Sele Teriparatide Acetate, terlakiren, terlipressin, terodiline, nomethionine Se 75, Selfotel, sematilide, Semduramicin, Teroxalene Hydrochloride, Teroxirone, tertatolol, Tesicam, Semotiadil, Semustine, Sense oligonucleotides, Sepazonium Tesimide, TeStolactone, Testosterone, Tetracaine, tetrachlo Chloride, Seperidol Hydrochloride, Seprilose, Seproxetine rodecaoxide, Tetracycline, Tetrahydrozoline Hydrochloride, Hydrochloride, Seractide Acetate, Sergolexole Maleate, Tetramisole Hydrochloride, Tetrazolast Meglumine, tetra Serine, Sermetacin, Sermorelin Acetate, Sertaconazole, Zomine, TetrofoSmin, Tetroquinone, TetroXoprim, Tetry Sertindole, Sertraline, Setiptiline, Setoperone, Sevirumab, damine, thaliblastine, Thalidomide, Theofibrate, Theophyl sevoflurane, sezolamide, Sibopirdine, Sibutramine Hydro line, Thiabendazole, Thiamiprine, Thiamphenicol, chloride, Signal transduction inhibitors, Silandrone, Silipide, Thiamylal, Thiazesim Hydrochloride, Thiazinamium Chlo Silteplase, Silver Nitrate, Simendan, SimtraZene, Simvasta ride, Thiethylperazine, Thimerfonate Sodium, Thimerosal, tin, Sincalide, Sinefungin, Sinitrodil, Sinnabidol, Sipatrigine, thiocoraline, thiofedrine, Thioguanine, thiomarinol, Thio Sirolimus, Sisomicin, Sitogluside, sizofiran, Sobu ZOxane, pental Sodium, thioperamide, Thioridazine, Thiotepa, Thio Sodium Amylosulfate, Sodium Iodide I 123, Sodium Nitro thixene, Thiphenamil Hydrochloride, Thiphencillin Potas prusside, Sodium Oxybate, Sodium phenylacetate, Sodium sium, Thiram, Thozalinone, Threonine, Thrombin, Salicylate, Solverol, Solypertine Tartrate, Somalapor, thrombopoietin, thrombopoietin mimetic, thymalfasin, thy Somantadine Hydrochloride, Somatomedin B, Somatomedin mopoietin receptor agonist, thymotrinan, Thyromedan C, Somatrem, Somatropin, Somenopor, Somidobove, Soner Hydrochloride, Thyroxine 1 125, Thyroxine 1 131, Tiac min, Sorbinil, Sorivudine, Sotalol, Soterenol Hydrochloride, rilast, Tiacrilast Sodium, tiagabine, Tiamenidine, tianeptine, Sparfloxacin, Sparfosate Sodium, Sparfosic acid, SparSomy tiapa?ant, Tiapamil Hydrochloride, Tiaramide Hydrochlo cin, Sparteine Sulfate, Spectinomycin Hydrochloride, Spi ride, Tiazofurin, Tibenelast Sodium, Tibolone, Tilbric Acid, camycin D, Spiperone, Spiradoline MeSylate, Spiramycin, Ticabesone Propionate, Ticarbodine, Ticarcillin Cresyl Spirapril Hydrochloride, Spiraprilat, Spirogermanium Sodium, Ticlatone, ticlopidine, Ticrynafen, tienoXolol, Tifu Hydrochloride, Spiromustine, Spironolactone, Spiroplatin, rac Sodium, Tigemonam Dicholine, Tigestol, Tiletamine SpiroXaSone, Splenopentin, Spongistatin 1, Sprodiamide, Hydrochloride, Tilidine Hydrochloride, tilisolol, tilnoprofen squalamine, Stallimycin Hydrochloride, Stannous Pyro arbamel, Tilorone Hydrochloride, Tiluldronate Disodium, phosphate, Stannous Sulfur Colloid, Stanozolol, Statolon, tiludronic acid, Timefurone, Timobesone Acetate, Timolol, Staurosporine, Stavudine, Steffimycin, , tin ethyl etiopurpurin, Tinabinol, Tinidazole, Tinzaparin Stepronin, Stilbazium Iodide, Stilonium Iodide, Stipiamide, Sodium, Tioconazole, Tiodazosin, Tiodonium Chloride, Tio Stiripentol, Stobadine, Streptomycin Sulfate, StreptonicOZid, peridone Hydrochloride, Tiopinac, Tiospirone Hydrochlo Streptonigrin, Streptozocin, Stromelysin inhibitors, Stron ride, Tiotidine, tiotropium bromide, Tioxidazole, Tipentosin tium Chloride Sr 89, succibun, Succimer, Succinylcholine Hydrochloride, Tipredane, Tiprenolol Hydrochloride, Tipri Chloride, Sucralfate, Sucrosofate Potassium, Sudoxicam, nast Meglumine, Tipropidil Hydrochloride, Tiqueside, Sufentanil, Sufotidine, Sulazepam, Sulbactam Pivoxil, Sul Tiquinamide Hydrochloride, tirandaly digin, Tirapazamine, conazole Nitrate, Sulfabenz, Sulfabenzamide, Sulfaceta tirilazad, tirofiban, tiropramide, titanocene dichloride, Tix mide, Sulfacytine, Sulfadiazine, Sulfadoxine, Sulfalene, anox, Tixocortol Pivalate, Tizanidine Hydrochloride, Tobra Sulfamerazine, Sulfameter, Sulfamethazine, Sulfamethizole, mycin, Tocainide, Tocamphyl, Tofenacin Hydrochloride, Sulfamethoxazole, Sulfamonomethoxine, Sulfamoxole, Sul Tolamolol, Tolazamide, Tolazoline Hydrochloride, Tolbuta fanilate Zinc, Sulfanitran, SulfaSalazine, SulfaSomizole, Sul mide, Tolcapone, Tolciclate, Tolfamide, Tolgabide, lamot fazamet, Sulfinalol Hydrochloride, sulfinosine, Sulfinpyra rigine, Tolimidone, Tolindate, Tolimetin, Tolnaftate, Tolpovi ZOne, Sulfisoxazole, Sulfomyxin, Sulfonterol done 1 131, Tolpyrramide, Tolrestat, Tomelukast, Hydrochloride, Sulfoxamine, Sulinldac, Sulmarin, Sulnida Tomoxetine Hydrochloride, Tonazocine Mesylate, Topira Zole, Suloctidil, Sulofenur, Sulopenem, Suloxifen Oxalate, mate, topotecan, Topotecan Hydrochloride, topSentin, Sulpiride, Sulprostone, Sultamicillin, Sulthiame, Sultopride, Topterone, Toquizine, toraSemide, toremifene, Torsemide, Sulukast, Sumarotene, Sumatriptan, Suncillin Sodium, ToSifen, ToSufloxacin, totipotent Stem cell factor, Traca Suproclone, Suprofen, Suradista, Suramin, Surfomer, Suric Zolate, trafermin, Tralonide, Tramadol Hydrochloride, Tra ainide Maleate, Suritozole, Suronacrine Maleate, Suxemerid maZoline Hydrochloride, trandolapril, TraneXamic Acid, Sulfate, Swainsonine, Symakalim, Symclosene, Symetine Tranilast, Transcainide, translation inhibitors, traXanox, Tra Hydrochloride, Synthetic glycosaminoglycans, Taciamine Zodone Hydrochloride, Trazodone-HCL, Trebenzomine Hydrochloride, Tacrine Hydrochloride, Tacrolimus, Hydrochloride, Trefentanil Hydrochloride, Treloxinate, Talampicillin Hydrochloride, Taleranol, Talisomycin, talli Trepipam Maleate, , tretinoin, Triacetin, mustine, Talmetacin, Talniflumate, Talopram Hydrochlo triacetyluridine, Triafungin, Triamcinolone, Triampy Zine ride, Talosalate, Tametraline Hydrochloride, Tamoxifen, Sulfate, Triamterene, Triazolam, Tribenoside, tricaprilin, Tampramine Fumarate, Tamsulosin Hydrochloride, Tan Tricetamide, Trichlormethiazide, trichohyalin, triciribine, damine Hydrochloride, tandoSpirone, tapgen, taprostene, Tricitrates, Triclofenol Piperazine, Triclofos Sodium, Tri TaSOSartan, tauromustine, Taxane, Taxoid, Tazadolene Suc clonide, trientine, Trifenagrel, triflavin, Triflocin, Trifluba cinate, taZanolast, tazaroteine, Tazifylline Hydrochloride, Zam, Triflumidate, Trifluoperazine Hydrochloride, Triflu TaZobactam, Tazofelone, Tazolol Hydrochloride, peridol, Triflu promazine, Triflu promazine Hydrochloride, Tebufelone, Tebuculine, Technetium Tc 99 m Bicisate, Teclo Trifluridine, Trihexyphenidyl Hydrochloride, Trilostane, Zan, Tecogalan Sodium, Teecleukin, Teflurane, Tegafur, TrimaZOsin Hydrochloride, trimegestone, Trimeprazine Tar Tegretol, Teicoplanin, telenzepine, tellurapyrylium, telm trate, Trimethadione, Trimethaphan Camsylate, Tri esteine, telmisartan, telomerase inhibitors, Teloxantrone methobenzamide Hydrochloride, Trimethoprim, Trime US 2006/OO18933 A1 Jan. 26, 2006 toZine, Trimetrexate, Trimipramine, Trimoprostil, cellulose, cellulose acetate, cellulose propionate (lower, Trimoxamine Hydrochloride, Triolein 1125, Triolein 1131, medium or higher molecular weight), cellulose acetate pro Trioxifene Mesylate, Tripamide, Tripelennamine Hydro pionate, cellulose acetate butyrate, cellulose acetate phtha chloride, Triprolidine Hydrochloride, Triptorelin, Trisul late, cellulose triacetate, poly(methyl methacrylate), poly fapyrimidines, Troclosene Potassium, troglitaZone, Trola (ethyl methacrylate), poly(butyl methacrylate), mine, Troleandomycin, trombodipine, trometamol, poly(isobutyl methacrylate), poly(hexyl methacrylate), Tropanserin Hydrochloride, Tropicamide, tropine ester, tro poly(isodecyl methacrylate), poly(lauryl methacrylate), pisetron, trospectomycin, trovafloxacin, troVirdine, Tryp poly(phenyl methacrylate), poly(methyl acrylate), poly(iso tophan, Tuberculin, Tubocurarine Chloride, Tubulozole propyl acrylate), poly(isobutyl actylate), poly(octadecyl Hydrochloride, tucarcsol, tulobuterol, turosteride, Tybam ate, tylogenin, Tyropanoate Sodium, Tyrosine, Tyrothricin, acrylate), waxes Such as beeswax, carnauba wax, microc tyrphostins, ubenimex, Uldazepam, Undecylenic Acid, rystalline wax, and OZokerite; fatty alcohols Such as ceto Uracil Mustard, urapidil, Urea, Uredepa, uridine triphos Stearyl alcohol, Stearyl alcohol, cetyl alcohol and myristyl phate, Urofollitropin, Urokinase, Ursodiol, Valaciclovir, alcohol; and fatty acid esterS Such as glyceryl monoStearate; Valine, Valnoctamide, Valproate Sodium, Valproic Acid, glycerol monooleate, acetylated monoglycerides, triStearin, Valsartan, Vamicamide, Vanadeine, Vancomycin, Vaninolol, tripalmitin, cetyl esters wax, glyceryl palmitostearate, glyc Vapi.prost Hydrochloride, Vapreotide, variolin B, Vaso eryl behenate and hydrogenated castor oil. pressin, Vecuronium Bromide, velaresol, Velnacrine Male 34. A dosage form according to claim 33, wherein the ate, Venlafaxine, Veradoline Hydrochloride, Veramine, Vera hydrophobic release controlling agents are Selected prefer pamil Hydrochloride, verdins, Verilopam Hydrochloride, ably from ammonio methacrylate co-polymers. Verlukast, Verofylline, Veroxan, Verteporfin, Vesnarinone, 35. A dosage form according to claim 34, wherein the vexibinol, Vidarabine, vigabatrin, Viloxazine Hydrochlo preferred from ammonio methacrylate co-polymers prefer ride, Vinblastine Sulfate, vinburnine citrate, Vincofos, vin ably from Eudragit RS (Ammonio Methacrylate Copolymer conate, Vincristine Sulfate, Vindesline, Vindesline Sulfate, type B USP), Eudragit RL (Ammonio Methacrylate Copoly Vinepidine Sulfate, Vinglycinate Sulfate, Vinleurosine Sul mer type A USP) and Eudragit NE30D (Polyacrylate dis fate, Vinorelbine, Vinpocetine, Vintoperol, VinXaltine, Vinzo lidine Sulfate, Viprostol, Virginiamycin, Viridofulvin, persion 30% Ph. Eur). ViroXime, Vitaxin, Volazocine, Voriconazole, Vorozole, VOX 36. A dosage form according to claim 31,wherein in micro ergolide, Warfarin Sodium, Xamoterol, Xanomeline, Xan matrix particles, metformin hydrochloride and one or more Oxate Sodium, Xanthinol Niacinate, Xemilofiban, Xenalipin, hydrophobic release controlling agents are present in a ratio Xenbucin, Xilobam, Ximoprofen, Xipamide, Xorphanol of from 100:1 to 100:75. Mesylate, Xylamidine Tosylate, Xylazine Hydrochloride, 37. A dosage form according to claim 36,wherein in micro Xylometazoline Hydrochloride, Xylose, yangamblin, Zab matrix particles, metformin hydrochloride and one or more icipril, Zacopride, Zafirlukast, Zalcitabine, Zaleplon, hydrophobic release controlling agents are present prefer ZaloSpirone, Zaltidine Hydrochloride, Zaltoprofen, Zan ably in a ratio of from 100:2.5 to 100:50. amivir, Zankiren, Zanoterone, Zantac, Zarirlukast, Zatebra 38. A dosage form according to claim 36, wherein in dine, Zatosetron, Zatosetron Maleate, Zenarestat, Zenazocine micro matrix particles, metformin hydrochloride and one or MeSylate, Zeniplatin, Zeranol, Zidometacin, Zidovudine, more hydrophobic release controlling agents are present Zifrosilone, Zilantel, Zilascorb, Zileuton, Zimeldine Hydro more preferably in a ratio of from 100:2.5 to 100:30. chloride, Zinc Undecylenate, Zindotrine, Zinoconazole Hydrochloride, Zinostatin, Zinterol Hydrochloride, Zin 39. A dosage form according to claim 36, wherein in ViroXime, Ziprasidone, Zobolt, Zofenopril Calcium, Zofeno micro matrix particles, metformin hydrochloride and one or prilat, Zolamine Hydrochloride, Zolazepam Hydrochloride, more hydrophobic release controlling agents are present Zoledronie acid, Zolertine Hydrochloride, Zolmitriptan, most preferably in a ratio of from 100:2.5 to 100:20. Zolpidem, Zomepirac Sodium, Zometapine, ZonicleZole 40. A dosage form according to claim 31, wherein in Hydrochloride, Zonisamide, Zopiclone, Zopolrestat, Zorba micro matrix particles, metformin hydrochloride can be leSS mycin, Zorubicin Hydrochloride, Zotepine, Zucapsaicin and than or equal to 1500 mg. pharmaceutically acceptable Salts thereof. 41. A dosage form according to claim 31, wherein the 30. A dosage form as claimed in claim 27, wherein said hydrophobic release controlling agents employed for coat dosage form is in the form of a multilayred tablet or a coated ing the Said micro matrix are Selected from the group tablet or a tablet in tablet or a capsule. comprising ammonio methacrylate copolymers type A and B 31. A modified release dosage form comprising of a as described in USP, methacrylic acid copolymer type A, B metformin hydrochloride prepared by using dual retard and C as described in USP polyacrylate dispersion 30% as technique to control the release of metformin, Said dosage described in Ph. Eur.polyvinyl acetate dispersion, ethylcel form comprising a) micro matrix particles containing met lulose, cellulose acetate, cellulose propionate (lower, formin hydrochloride and one or more hydrophobic release medium or higher molecular weight), cellulose acetate pro controlling agent and b) coating of one or more hydrophobic pionate, cellulose acetate butyrate, cellulose acetate phtha release controlling agent on micro matrix particles. late, cellulose triacetate, poly(methyl methacrylate), poly 32. A dosage form as claimed in claim 31, is in the form (ethyl methacrylate), poly(butyl methacrylate), of tablet. poly(isobutyl methacrylate), poly(hexyl methacrylate), 33. A dosage form according to claim 31, wherein the poly(isodecyl methacrylate), poly(lauryl methacrylate), hydrophobic release controlling agents employed for the poly(phenyl methacrylate), poly(methyl acrylate), poly(iso micro matrix particles are Selected from the group compris propyl acrylate), poly(isobutyl actylate), poly(octadecyl ing of ammonio methacrylate copolymers type A and B as acrylate), waxes Such as beeswax, carnauba wax, microc described in USP, methacrylic acid copolymer type A, B and rystalline wax, and OZokerite; fatty alcohols Such as ceto C as described in USP, polyacrylate dispersion 30% as Stearyl alcohol, Stearyl alcohol, cetyl alcohol and myristyl described in Ph. Eur., polyvinyl acetate dispersion, ethyl alcohol; and fatty acid esterS Such as glyceryl monoStearate; US 2006/OO18933 A1 Jan. 26, 2006 32 glycerol monooleate, acetylated monoglycerides, triStearin, 50. A dosage form according to claim 31, is used for tripalmitin, cetyl esters wax, glyceryl palmitoStearate, glyc human beings. eryl behenate and hydrogenated castor oil. 51. A dosage form according to claim 31, wherein the 42. A dosage form according to claim 41, wherein the hydrophobic release controlling agents is Selected from fatty maximum plasma metformin concentration is achieved acid esters. between 700 ng/ml and 2500 ng/ml. 43. A dosage form according to claim 41, wherein the 52. A dosage form according to claim 51, wherein the hydrophobic release controlling agents are Selected from the maximum plasma metformin concentration is achieved pref group comprising of hydrogenated castor oil and glycerol erably between 900 ng/ml and 2400 ng/ml. distearate. 53. A dosage form according to claim 52, wherein the 44. A dosage form according to claim 31, micro matrix maximum plasma metformin concentration is achieved particles and coating of one or more hydrophobic release more preferably between 1000 ng/ml and 2350 ng/ml. controlling agents are present in a ratio of from 100:0.5 to 54. A dosage form according to claim 31, wherein the 100:75. 45. A dosage form according to claim 44, wherein micro modified release metformin formulation for once daily matrix particles and coating of one or more hydrophobic administration exhibit invivo mean dissolution time (MDT) release controlling agents are preferably present in a ratio of of approximately 4 hours to 6 hours. from 100:1 to 100:50. 55. A dosage form according to claim 31, wherein the 46. A dosage form according to claim 45, wherein micro minimum plasma metformin concentration (at 24 hours) matrix particles and coating of one or more hydrophobic ranges between 0 and 450 ng/ml after oral administration. release controlling agents are more preferably present in a 56. A dosage form as claimed in claim 1, wherein the Said ratio of from 100:2.5 to 100:20. dosage form is used to increase the payload of high Solu 47. A modified release dosage form according to claim 31, bility active ingredient. wherein the composition of the micromatrix particles and 57. A dosage form as claimed in claim 31, wherein the coated micromatrix particles is as follows Said dosage form is used to increase the payload of met formin hydrochloride. Micro matrix particles 58. A dosage form as claimed in claim 1, wherein the Said dosage form may optionally contain more than one high Metformin hydrochloride 75% w/w to 99% w/w Eudragit RS 1% w/w to 25% w/w solubility active ingredient. Coated micro matrix particles 59. A dosage form as claimed in claim 31, wherein the Said dosage form may optionally contain more than one Micro matrix particles Hydrogenated castor oil antidiabetic active ingredient. Magnesium stearate 60. A proceSS for the preparation of a modified release dosage form comprising a) preparing a micro matrix par 48. A dosage form according to claim 31, wherein the ticles containing metformin hydrochloride and one or more dissolution of metformin hydrochloride is not more than hydrophobic release controlling agent and b) coating the 50% in 1 hour, from 30 to 90% in four hours and not less Said micro matrix particles containing metformin hydrochlo than 65% in twelve hours. ride and one or more hydrophobic release controlling agent. 49. A dosage form according to claim 31, is once a day oral formulation.