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US 2003O180357A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2003/0180357 A1 Martino et al. (43) Pub. Date: Sep. 25, 2003

(54) PHARMACEUTICAL TABLET Related U.S. Application Data (60) Provisional application No. 60/355,705, filed on Feb. (76) Inventors: Alice C. Martino, Kalamazoo, MI 7, 2002. (US); Robert M. Noack, Grand Rapids, MI (US); Steven A. Pierman, Portage, Publication Classification MI (US) (51) Int. Cl...... A61K 9/20: A61K 9/34 (52) U.S. Cl...... 424/465; 424/481 Correspondence Address: PHARMACIA CORPORATION (57) ABSTRACT GLOBAL PATENT DEPARTMENT POST OFFICE BOX 1027 A pharmaceutical tablet is provided comprising a core and a ST. LOUIS, MO 63006 (US) coating adherent thereto, wherein (a) the core comprises Solid particles of a water-Soluble dye distributed in a matrix, and (b) the coating comprises gellan gum. The tablet is (21) Appl. No.: 10/359,939 Suitable for peroral or intraoral administration, for example for delivery of a drug contained in the core of the tablet to a Subject. The tablet has a Speckled appearance that renders (22) Filed: Feb. 6, 2003 the tablet readily identifiable. US 2003/0180357 A1 Sep. 25, 2003

PHARMACEUTICAL TABLET and dissolves to release . Gellan Sodium Salt is listed among hydrocolloids Said to be useful in Such film 0001. This application claims priority of U.S. provisional dosage forms. application Serial No. 60/355,705 filed on Feb. 7, 2002. 0009 U.S. Pat. No. 6,291.506 to Levin, incorporated FIELD OF THE INVENTION herein by reference, discloses that the ophthalmic drug can be formulated for ocular administration by 0002 The present invention relates to orally deliverable Suspending it in an agent Such as gellan gum that will pharmaceutical dosage forms, more particularly tablets. increase corneal contact time with the drug. Other possible delivery modes for the drug are contemplated therein. A BACKGROUND OF THE INVENTION claim is included to a method wherein the drug is delivered by a Selection of routes including Sublingually. 0.003 Tablets are the most common and convenient phar maceutical dosage form for oral administration of medica SUMMARY OF THE INVENTION tions. It is an important functional attribute of a tablet that it be readily identifiable by appearance, including by Size, 0010. There is now provided a pharmaceutical tablet shape, Surface texture, markings and color. Such ready comprising a core and a coating adherent thereto, wherein identifiability is important in minimizing dispensing errors (a) the core comprises Solid particles of a water-Soluble dye and in enabling patients on multiple to distin distributed in a matrix, and (b) the coating comprises gellan guish among the drugs they take at different times or gum. frequencies. A vast array of drugs are now formulated as 0011. The tablet is particularly suitable for peroral or tablets, many of these drugs being formulated at different intraoral administration, for example for delivery of a drug dosage Strengths, and it is therefore becoming ever more contained in the core of the tablet to a Subject, illustratively important, yet ever more difficult to insure, that any new a human subject. The term “peroral herein refers to admin tablet has unique appearance. istration via the mouth involving Swallowing of the tablet 0004. In particular, the range of readily distinguishable without substantial prior disintegration of the tablet in the colors available to the formulator of tablets is rather limited. mouth, So that absorption of the drug typically occurs in the To some extent this problem has been alleviated by use of gastrointestinal tract. The term “intraoral herein refers to particolored, bicolored or multicolored tablets. However, a administration by placement of the tablet in the mouth of the need remains in the art for tablets having unique Surface Subject, where the tablet disintegrates and/or dissolves, So color patterns. that absorption of the drug typically occurs at least in part via the oral mucosa. For intraoral administration, the tablet 0005. In the case of coated tablets, color can be an can be placed in or on any part of the mouth, but placement attribute of the Surface coating. For example, a range of of the tablet in the Sublingual or buccal Spaces is preferred. opaque pigments are available for incorporation in tablet coating compositions Such as those based on ethylcellulose; 0012. The tablet can alternatively be dissolved or dis these pigments tend to impart a Solid white or colored persed in a liquid vehicle, preferably water, and Swallowed appearance to a coated tablet. Alternatively, the Surface as a draft. coating can be clear and transparent, and the color of the 0013 Tablets of the invention have an unusual speckled coated tablet is controlled by the color of the tablet core appearance. Without being bound by theory, it is believed underlying the coating. that during the process of coating the core with an aqueous 0006 U.S. Pat. No. 6,326,028 to Nivaggioli et al., incor coating composition comprising gellan gum, dye particles in porated herein by reference, discloses a tablet coating com contact with the coating composition partially dissolve, prising gellan gum. Such a coating is Said to be useful for causing color to "bleed' into the coating at the locus of each tablets to be taken orally, and to confer benefits in appear Such particle. The color then becomes fixed as the coating ance, identification, mouth feel, reduced dust, Stability, color dries. The Speckled pattern is accentuated and rendered even and/or Swallowability. more attractive or elegant by a high gloSS Surface texture contributed by the gellan gum. AS described more fully 0007 International Patent Publication No. WO 01/10406, hereinbelow, many variants of the Speckled pattern charac incorporated herein by reference, discloses compositions teristic of tablets of the invention are possible and practi Said to be Suitable for a wide range of routes of adminis cable, adding a new option to the formulator Seeking to tration of Sildenafil citrate, including buccal and Sublingual prepare a readily identifiable tablet. routes. Preferred compositions disclosed are said to com 0014. As a further advantage, the speckled pattern of prise a Solution, gel, Semisolid, Suspension, metered dose device, transdermal patch or film. It is indicated that Such tablets of the invention can obscure any Small areas of compositions can include a gelling System, for example discoloration that can Sometimes result from variation in gellan gum 0.5% to 10%. process conditions. 0015. Other features, advantages and benefits of the 0008 International Patent Publication No. WO 02/05820, invention will be apparent from the description that follows. incorporated herein by reference, discloses film dosage forms comprising Sildenafil citrate. These dosage forms are DETAILED DESCRIPTION OF THE prepared by mixing a Solid dispersion of Sildenafil citrate INVENTION and a water-Soluble Sugar with a hydrocolloid and optionally other ingredients, and are Said, upon placement on a mucosal 0016 A tablet of the invention can be a placebo tablet, Surface, to form a coating that Subsequently disintegrates i.e., containing no drug or other active agent in the core US 2003/0180357 A1 Sep. 25, 2003

thereof. Preferably a tablet of the invention contains in the nine, norcotinine, nornicotine, N-oxide, core a therapeutically and/or prophylactically useful amount N-oxide, 3-hydroxycotinine and 5-hydroxycotinine), of a drug, more preferably a drug that is advantageously , and metabolites thereof (e.g., the delivered by peroral or intraoral administration. erythro- and threo-amino of bupropion, the erythro 0017 For example, a drug present in the core of a tablet amino diol of bupropion and ), , of the invention can be selected from the following illus Selegiline, and its 9-hydroxy metabolite, desm trative classes: ACE inhibitors, C.- , ethylselegiline, Substituted derivatives (e.g., 1-(6- B-adrenergic agonists, C.-adrenergic blockers, B-adrenergic chloro-3-pyridinyl)methyl-2-imidazolidine, 1-(6-chloro-3- blockers (beta blockers); deterrents, aldose reduc pyridinyl)methyl-2-imidazothiazole and analogs thereof), tase inhibitors, aldosterone antagonists, amino acids, ana methcamylamine, , , , tri bolics; (both narcotic and non-narcotic); anes methaphan, trimethaphan camsylate, , 2-(3-chlo thetics, anorexicS, antacids, anthelmintics, antiacne agents, rophenyl)-3,5,5-trimethyl-2-morpholinol, (e.g., antiallergics, antiandrogens, agents, antianxiety isovaleramide), Y-vinyl GABA (GVG), epibatidine and agents, antiarrythmics, antiasthmatics, antibacterial agents derivatives thereof, 7-azabicyclo-2.2.1-heptane and -hep and antibiotics, antialopecia and antibaldness agents, anti tene compounds, , , , hexam amebics, antibodies, drugs, anticoagulants ethonium, , dihydro-3-erythroidine, erySodine, and blood thinners, anticolitis drugs, , anti d-tubocurarine, , , , cystitis drugs, , antidiabetic agents, antidiar hetero-oxy alkanamines, benzylidene- and cinnamylidene rheals, antidiuretics, antidotes, antiemetics, antieStrogens, antiflatulents, antifungal agents, antigens, antiglaucoma anabasines, azaindole-ethylamine derivatives, N-(pyridinyl agents, antihistaminics, antihyperactives, antihyperlipopro methyl)-heterocyclylideneamines and NK-1 teinemics, antihypertensives, antihyperthyroid agents, anti antagonists (e.g., 9-bromo-1,2,3,4,5,6-hexahydro-1,5- hypotensives, antihypothyroid agents, anti-infectives, anti methano-pyrido1,2-a1,5diazocin-8-one). inflammatories (both Steroidal and nonsteroidal); 0021. In another embodiment a drug contained in the core antimalarial agents, antimigraine agents, antineoplastics; of the tablet is an antibacterial drug. Illustratively Such a antiobesity agents, antiparkinsonian agents and antidyski drug can be an antibiotic, for example an aminoglycoside, netics, antipneumonia agents, antiprotozoal agents, antipru amphenicol, ansamycin, carbapenem, cephalosporin, cepha ritics, antipsoriatics, antipsychotics, antipyretics, antirheu mycin, monobactam, oxacephem, penicillin, lincosamide, matics, antisecretory agents, anti-Shock , macrollide, polypeptide or tetracycline; or a Synthetic anti antispasmodics, antithrombotics; antitumor agents, antitus bacterial, for example a 2,4-diaminopyrimidine, nitrofuran, Sives, antiulceratives, antiviral agents, anxiolytics, bacteri Oxazolidinone, quinolone or analog thereof, Sulfonamide or cidins, bone densifiers, bronchodilators, sulfone. Presently preferred antibacterials include the fol blockers, carbonic anhydrase inhibitors, cardiotonics and lowing illustrative examples: amikacin, azithromycin, heart , chemotherapeutics, choleretics, cholin cefixime, cefoperaZone, cefotaxime, ceftazidime, cefti ergics, chronic fatigue Syndrome medications, CNS Stimu ZOXime, ceftriaxone, chloramphenicol, , clin lants, coagulants, contraceptives, cystic fibrosis medica damycin, colistin, domeclocycline, doxycycline, erythromy tions, decongestants, diuretics, receptor agonists, cin, gentamicin, lincomycin, lineZolid, mafenide, dopamine receptor antagonists, enzymes, estrogens, expec methacycline, minocycline, neomycin, norfloxacin, ofloxa torants, gastric hyperactivity medications, glucocorticoids, cin, oxytetracycline, pirlimycin, polymyxin B, hemostatics; HMG CoA reductase inhibitors; hormones; pyrimethamine, Silver Sulfadiazine, Sulfacetamide, Sulfisox hypnotics, immunomodulators, immunosuppressants, laxa azole, tetracycline, tobramycin, trimethoprim and combina tives, medicaments for oral and periodontal diseases, miot tions thereof. In one embodiment an antibacterial drug ics, monoamine oxidase inhibitors, mucolytics, multiple present in the core of the tablet is an oxazolidinone, for Sclerosis medications, muscle relaxants, mydriatics, narcotic example selected from (S)-N-3-3-fluoro-4-4-(hydroxy antagonists, NMDA receptor antagonists, oligonucleotides, acetyl)-1-piperazinylphenyl-2-oxo-5-oxazolidinylme ophthalmic drugs, oxytocics, peptides, polypeptides and thyl)acetamide (eperezolid), (S)-N-3-3-fluoro-4-4-(mor proteins; polysaccharides, , prostaglandins, pholinyl)phenyl)-2-oxo-5-oxazolidinyl)methyl)acetamide protease inhibitors, respiratory Stimulants, Sedatives, Sero (linezolid), N-(5S)-3-3-fluoro-4-4-(2-fluoroethyl)-3-oxo tonin uptake inhibitors, SeX hormones including androgens, 1-piperazinylphenyl-2-oxo-5-oxazolidinyl)methyl)aceta Smoking cessation drugs, Smooth muscle relaxants, Smooth mide, (S)-N-3-5-(3-pyridyl)thiophen-2-yl)-2-oxo-5-ox muscle Stimulants, thrombolytics, tranquilizers, urinary azolidinyl)methyl)acetamide, and (S)-N-3-5-(4- acidifiers, urinary incontinence medications, vasodilators, pyridyl)pyrid-2-yl)-2-oxo-5-oxazolidinyl)methyl)acetamide Vasoprotectants, and combinations thereof. hydrochloride. 0.018. It will be understood that any reference herein to a particular drug compound includes tautomers, Stereoiso 0022. In another embodiment a drug contained in the core mers, Salts and of that compound and is not specific of the tablet is an antimigraine agent. Illustratively Such an to any one Solid State form of the drug. agent is an alkylxanthine, for example ; a dopamine D receptor , for example alpiropride or ; a 0019. In one embodiment a drug contained in the core of GABA , for example ganaxolone; a the tablet is a Smoking cessation drug, for example nicotine, 5-hydroxytriptamine (5-HT) receptor agonist, for example a nicotine metabolite or a non-nicotine aid to Smoking , , , , , cessation Such as bupropion or ibogaine. or ; ergot or a derivative thereof, for 0020 Illustratively, a smoking cessation drug can be example or ; or a vasomodu Selected from nicotine and metabolites thereof (e.g., coti lator, for example , fonazine or . US 2003/0180357 A1 Sep. 25, 2003

0023. In another embodiment a drug contained in the core Salicylate, , dimepheptanol, dimethylthiam of the tablet is useful in treating or preventing an ophthalmic butene, dioxaphetylbutyrate, , diprocetyl, dipy disorder. rone, ditazol, droxicam, emorfaZone, enfenamic acid, 0024 Illustratively such an ophthalmic drug can be an enoXolone, epirizole, , eterSalate, , antibacterial, for example Selected from the classes listed , ethoxazene, ethylmethylthiambutene, ethyl above. , , etofenamate, etonitaZene, , eugenol, felbinac, fenbufen, fenclozic acid, fendosal, feno 0.025 Alternatively or in addition, such an ophthalmic profen, , fentiazac, fepradinol, feprazone, floctafe drug can illustratively be an antiglaucoma or intraocular nine, fluazacort, flucloronide, , flumetha preSSure lowering agent, Such as (a) an O- Sone, flunisolide, flunixin, flunoxaprofen, fluocinolone or Sympathomimetic, e.g., adrenolone, , bri acetonide, fluocinonide, fluocortin butyl, fluocortolone, monidine or diplivefrin; (b) a f-adrenergic blocker, e.g., fluoresone, fluorometholone, fluperolone, , flu , , , , , bufe prednidene, fluprednisolone, fluproduaZone, flurandreno tolol, , , bunolol, , , lide, , formocortal, fosfosal, gentisic acid, glafe carvedilol, , deXpropanolol, , , nine, glucametacin, glycol Salicylate, guaiaZulene, , , , , oxyprenolol, halcinonide, halometasone, haloprednone, , , , , , , hydrocortamate, hydrocortisone, , hydroxy , , , or Vaninolol; (c) a , ibufenac, , ibuproxam, imidazole Sali carbonic anhydrase inhibitor, e.g., acetazolamide or dorZola cylate, indomethacin, indoprofen, isofeZolac, isoladol, mide; or (d) a prostaglandin or analog thereof, e.g., PGF , isonixin, isoxepac, , , analogS Such as bimatoprost, latanoprost, travoprost and , , p-lactophenetide, , levor unoprostone isopropyl. phanol, , lonazolac, , , 0026. Alternatively or in addition, such an ophthalmic acetylsalicylate, maZipredone, , drug can illustratively be a miotic, e.g., , phySOS medrySone, , meperidine, meprednisone, tigmine or pilocarpine. , meSalamine, , , methotri meprazine, methylprednisolone, metiazinic acid, metofo 0027) Alternatively or in addition, such an ophthalmic line, , mofebutaZone, mofeZolac, , mor drug can illustratively be an anti-inflammatory agent, for phine, morphine hydrochloride, morphine Sulfate, example an NSAID, more preferably a selective COX-2 morpholine Salicylate, myrophine, , , inhibitory drug, for example Selected from those listed 1-naphthyl Salicylate, , narceline, , nico below. morphine, , , , 5'-nitro 0028. In another embodiment a drug contained in the core 2'-propoxyacetanilide, norlevorphanol, normethadone, nor of the tablet is an , antipyretic or anti-inflammatory morphine, , olSalazine, , oxaceprol, agent, e.g., aceclofenac, , e-acetamidocaproic Oxametacine, , , , acid, acetamininophen, acetaminoSalol, , acetyl OxyphenbutaZone, papaveretum, paramethasone, para (), S-adenosylmethionine, alcofenac, nyline, , parSalmide, , perisoxal, phen alclometasone, , algestone, allylprodine, almino acetin, , , hydro profen, aloxiprin, alphaprodine, aluminum bis(acetylsalicy chloride, phenocol, , phenopyrazone, phenyl late), amcinonide, amfenac, aminochlorthenoxazin, acetylsalicylate, phenylbutaZone, phenyl Salicylate, 3-amino-4-hydroxybutyric acid, 2-amino-4-picoline, amino phenyramidol, piketoprofen, , pipebuZone, pip propylon, aminopyrine, amiXetrine, ammonium Salicylate, erylone, piprofen, piraZolac, , , prano ampiroXicam, amtolimetin guacil, anilleridine, antipyrine, , apaZone, beclomethasone, bendazac, benory profen, prednicarbate, prednisolone, prednisone, prednival, late, , benzpiperylon, , benzyl prednylidene, proglumetacin, , promedol, pro morphine, bermoprofen, betamethasone, , C.-bis pacetamol, , propoxyphene, , pro abolol, , p-bromoacetanilide, 5-bromosalicylic quaZone, protizinic acid, proxazole, ramifenaZone, remifen acid acetate, bromosaligenin, , bucloxic acid, buco tanil, rimazolium metilsulfate, , Salacetamide, lome, budeSonide, bufeXamac, bumadizon, , , , Salicylamide O-acetic acid, Salicylic butacetin, butibufen, butophanol, , carbi acid, Salicylsulfuric acid, , Salverine, Simetride, phene, carprofen, carSalam, , chlorobutanol, chlo , SulfaSalazine, , Superoxide dismutase, roprednisone, chlorthenoxazin, Salicylate, cin , SuxibuZone, talniflumate, tenidap, , chophen, cinmetacin, ciramadol, clidanac, clobetasol, clocortolone, clometacin, clonitaZene, clonixin, clopirac, terofenamate, , thiazolinobutaZone, tiaprofenic cloprednol, clove, , codeine methyl bromide, acid, tiaramide, , tinoridine, tiXocortol, tolfenamic codeine phosphate, codeine Sulfate, cortisone, cortivaZol, acid, , , triamcinolone, tropesin, Valde cropropamide, crotethamide, deflazacort, , coxib, , Xenbucin, Ximoprofen, or Zome deSonide, desoximetaSone, dexamethasone, deXOXadrol, pirac. , , diampromide, , dife namizole, difenpiramide, diflorasone, diflucortolone, 0029) In a particular embodiment Such a drug is a Selec , difluprednate, , dihydrocodeinone tive COX-2 inhibitory drug, for example a compound of enol acetate, , dihydroxyaluminum acetyl formula (I): US 2003/0180357 A1 Sep. 25, 2003

0038. In a preferred composition according to the present embodiment the selective COX-2 inhibitory drug is a com (I) pound having the formula (II): R11

(i. (II) R13 A. NR13 ^, O \, OY-N4 4 R121 V R15 \, N X

0030 or a thereof or a pharmaceutically accept R16 able Salt thereof, wherein: 0031) A is a substituent selected from partially 0039 where R' is a methyl, amino or imide group, R' unsaturated or unsaturated heterocyclyl and partially is hydrogen or a C- alkyl or alkoxy group, X is N or CR'' unsaturated or unsaturated carbocyclic rings, prefer where R7 is hydrogen or halogen, and Y and Z are inde ably a heterocyclyl group Selected from pyrazolyl, pendently carbon or nitrogen atoms defining adjacent atoms furanonyl, isoxazolyl, pyridinyl, cyclopentenonyl of a five- to six-membered ring that is unsubstituted or and pyridaZinonyl groups, Substituted at one or more positions with OXO, halo, methyl or halomethyl groups. Preferred such five- to six-membered 0032 X is O, S or CH; rings are cyclopentenone, furanone, methylpyrazole, isox 0033) n is 0 or 1; azole and pyridine rings Substituted at no more than one position. 0034) R' is at least one substituent selected from heterocyclyl, cycloalkyl, cycloalkenyl and aryl, and 0040. In another preferred composition according to the is optionally Substituted at a Substitutable position present embodiment the selective COX-2 inhibitory drug is with one or more radicals Selected from alkyl, a compound having the formula (III): haloalkyl, cyano, carboxyl, alkoxycarbonyl, hydroxyl, hydroxyalkyl, haloalkoxy, amino, alky lamino, arylamino, nitro, alkoxyalkyl, alkylsulfinyl, (III) halo, alkoxy and alkylthio; R19 0035) R' is methyl, amino or aminocarbonylalkyl; R2 COOH 0036) R' is one or more radicals selected from hydrido, halo, alkyl, alkenyl, alkynyl, OXO, cyano, carboxyl, cyanoalkyl, heterocyclyloxy, alkyloxy, alkylthio, alkylcarbonyl, cycloalkyl, aryl, haloalkyl, heterocyclyl, cycloalkenyl, aralkyl, heterocyclyla lkyl, acyl, alkylthioalkyl, hydroxyalkyl, alkoxycar bonyl, arylcarbonyl, aralkylcarbonyl, aralkenyl, 0041 or a prodrug thereof or a pharmaceutically accept alkoxyalkyl, arylthioalkyl, aryloxyalkyl, aralkylthio able salt thereof, where X" is O, S or N-lower alkyl; R is alkyl, aralkoxyalkyl, alkoxyaralkoxyalkyl, alkoxy lower haloalkyl; R' is hydrogen or halogen; R is hydro carbonylalkyl, aminocarbonyl, aminocarbonylalkyl, gen, halogen, lower alkyl, lower alkoxy or haloalkoxy, lower alkylaminocarbonyl, N-arylaminocarbonyl, N-alkyl aralkylcarbonyl, lower dialkylaminoSulfonyl, lower alky N-arylaminocarbonyl, alkylaminocarbonylalkyl, laminoSulfonyl, lower aralkylaminoSulfonyl, lower het carboxyalkyl, alkylamino, N-arylamino, N-aralky eroaralkylaminoSulfonyl, or 5- or 6-membered nitrogen lamino, N-alkyl-N-aralkylamino, N-alkyl-N-ary containing heterocyclosulfonyl; and R'' and R’ are lamino, aminoalkyl, alkylaminoalkyl, N-arylami independently hydrogen, halogen, lower alkyl, lower noalkyl, N-aralkylaminoalkyl, N-alkyl-N- alkoxy, or aryl. aralkylaminoalkyl, N-alkyl-N-arylaminoalkyl, aryloxy, aralkoxy, arylthio, aralkylthio, alkylsulfinyl, 0042 A particularly useful compound of formula (III) is alkylsulfonyl, aminoSulfonyl, alkylaminoSulfonyl, (S)-6,8-dichloro-2-(trifluoromethyl)-2H-1-benzopyran-3- N-arylaminosulfonyl, arylsulfonyl and N-alkyl-N- carboxylic acid. arylaminosulfonyl, R' being optionally substituted 0043. In yet another preferred composition according to at a Substitutable position with one or more radicals the present embodiment the selective COX-2 inhibitory drug Selected from alkyl, haloalkyl, cyano, carboxyl, is a 5-alkyl-2-arylaminophenylacetic acid or derivative alkoxycarbonyl, hydroxyl, hydroxyalkyl, thereof Particularly useful compounds of this class are haloalkoxy, amino, alkylamino, arylamino, nitro, 5-methyl-2-(2-chloro-6'-fluoroanilino)phenylacetic acid alkoxyalkyl, alkylsulfinyl, halo, alkoxy and alky and pharmaceutically acceptable Salts thereof. lthio; and 0044 Illustratively, celecoxib, deracoxib, , 0037) R' is selected from hydrido and halo. parecoxib, rofecoxib, etoricoxib, 2-(3,5-difluorophenyl)-3- US 2003/0180357 A1 Sep. 25, 2003

4-(methylsulfonyl)phenyl-2-cyclopenten-1-one, (S)-6,8- 0054) It is preferred that the compound of formula (V) or dichloro-2-(trifluoromethyl)-2H-1-benzopyran-3-carboxylic Salt thereof is water-soluble. acid, 2-(3,4-difluorophenyl)-4-(3-hydroxy-3-methyl-1-bu tyoxy)-5-4-(methylsulfonyl)phenyl)-3-(2H)-pyridazinone 0055 Pharmaceutically acceptable salts of a compound of formula (V) include without restriction salts of the and Salts thereof are useful in compositions of the invention. following acids: hydrochloric, hydrobromic, Sulfuric, meth 0.045 For example, the selective COX-2 inhibitory drug aneSulfonic, phosphoric, nitric, benzoic, citric, tartaric, or prodrug thereof can be selected from celecoxib, Valde fumaric and maleic acids, and mono- and dicarboxylic acids coxib, parecoxib, rofecoxib, etoricoxib, (S)-6,8-dichloro-2- of formula CH-(CH), COOH and HOOC-(CH), (trifluoromethyl)-2H-1-benzopyran-3-carboxylic acid and COOH where n is 0 to 4, for example malonic acid. salts thereof. 0056 Particularly preferred salts are the hydrochloride 0046. In another embodiment, a drug contained in the Salt and the maleate, i.e., (Z)-2-butenedioate, Salt. core of the tablet is useful in treatment and/or prevention of Sexual dysfunction in male and/or female Subjects. Such a 0057 Compounds of formula (V) and their salts can be drug can illustratively be (a) a phosphodiesterase type 5 prepared by processes known per se, including processes (PDE5) inhibitor, e.g., sildenafil, or , (b) described in patent literature cited herein. However, the a cyclic GMP phosphodiesterase inhibitor, (c) a cyclic AMP present invention is not restricted by the proceSS used to activator, (d) an O-, e.g., prepare the therapeutic agent. or , or (e) a dopaminergic agonist, e.g., apomor 0.058 Preferred compounds of formula (V) are those phine. Such a drug can be a compound of formula (V) below. disclosed generically or specifically in U.S. Pat. No. 5,273, Alternatively, a drug contained in the core of the tablet can 975 to Moon et al. Especially preferred compounds are those be other than a drug useful in treatment and/or prevention of Sexual dysfunction. AS another alternative, a drug contained of formula (VI) in the core of the tablet can be useful in treatment and/or prevention of Sexual dysfunction but is other than a com pound of formula (V) below. (VI) 0047. In illustrative compositions a drug useful for CH example in treatment of Parkinson's disease or Sexual dyS function is present in the core of the tablet and is a N compound of formula (V) N X

(V) 0059 wherein X is O or S, and pharmaceutically accept able salts thereof. 0060 Tablet cores useful according to the invention can be prepared by any Suitable process known in the art. A core according to the invention comprises a matrix wherein are distributed solid particles of a water-soluble dye. Any suit able excipient or excipients can form the matrix. For peroral tablets the matrix typically comprises a diluent or carrier, for 0.048 or a pharmaceutically acceptable salt thereof, example lactose and/or Starch, and can further comprise wherein additional excipients Such as binders, disintegrants, wetting agents, etc. For intraoral tablets the matrix typically com 0049) R', Rand Rare the same or different and are prises a water-Soluble Sugar, for example mannitol and/or H, C alkyl (optionally phenyl Substituted), Cs maltose. If a drug is present in the core, the drug, too, is alkenyl or alkynyl or Cso cycloalkyl, or where R distributed in the matrix. is as above and R' and R are cyclized with the attached N atom to form pyrrolidinyl, piperidinyl, 0061 The ultimate appearance of the tablet depends in morpholinyl, 4-methylpiperazinyl or imidazolyl part upon the Selection of water-Soluble dye and the number groupS, and size of the Solid particles of the dye. For example, relatively large particles will tend to produce a Speckled 0050 X is H, F, Cl, Br, I, OH, C, alkyl or alkoxy, pattern having larger blocks of color than will be produced CN, carboxamide, carboxyl or (C. alkyl)carbonyl, by Smaller particles, and a relatively large number of par ticles will tend to produce a Speckled pattern where the color 0051) A is CH, CH, CHF, CHC1, CHBr, CHI, covers a greater portion of the tablet Surface than will be CHCH, C=O, C-S, CSCH, C=NH, CNH, produced by fewer particles. A more water-soluble dye will CNHCH, CNHCOOCH, CNHCN, SO, or N; tend to produce larger and/or leSS discrete blocks of color 0.052 B is CH, CH, CHF, CHC1, CHBr, CHI, than will be produced by a less water-soluble dye. C=O, N, NH or NCH, and n is 0 or 1; and 0062 Optionally solid particles of more than one water 0053 D is CH, CH, CHF, CHC1, CHBr, CHI, Soluble dye can be present in the core, contributing a C=O, O, N, NH or NCH, bicolored or multicolored Speckled appearance to the tablet. US 2003/0180357 A1 Sep. 25, 2003

0.063. The core is coated with a coating composition 0070 Coating and cooling conditions can also affect the comprising gellan gum, as more filly described below. The precise color pattern of the finished tablet. For example, if coating is typically present in an amount representing a coating is done at lower temperatures and/or if cooling weight gain of about 0.1% to about 5%, but greater or lesser occurs slowly, So that the Solid dye particles in the core are amounts can be used if desired. Preferably the gellan gum exposed to water for a longer period of time, a Speckled constitutes about 25% to 100%, more preferably about 50% pattern with larger blocks of color will typically result. to 100%, by weight of the coating. 0071 An illustrative Sublingual tablet of the invention 0.064 Preferably the coating is an excipient coating. An containing as active agent a Salt, e.g., the maleate Salt, of “excipient coating herein is a coating consisting, at least at Sumanirole or (R)-5,6-dihydro-5-(methylamino)-4H-imi the time of application of the coating to the core, only of dazo4.5-ij-quinoline-2(1H)-thione has a core having the excipient materials, i.e., having Substantially no drug present following composition: therein. It will be understood that during manufacture and Storage Some migration of a drug Substance can potentially occur from the core to the coating of a tablet of the active agent 0.1-3% free base equivalent invention, but this is generally minimal. Thus a drug Sub mannitol 50-90% stance, if present in the tablet, is largely confined to the core powdered sorbitol 10-40% where it is not commingled with gellan gum. hydroxypropylcellulose 0-10% Xanthan gum O-5% 0065. Any gellan gum can be used in the coating com flavoring agent O-0.5% position, but it is preferred to use a deacylated gellan gum water-soluble dye O-0.5% such as that sold under the trademark KelcogelTM. Option colloidal silicon dioxide 0-1% ally one or more additional gums and/or biopolymers, for stearate O.5-5% example alginates, can be present in the coating composi all percentages being by weight. tion. 0.066 The coating composition comprises a sprayable 0072 Another illustrative sublingual tablet of the inven vehicle, preferably water, having dissolved or dispersed tion containing as active agent a Salt, e.g., the maleate Salt, therein a gellan gum and optionally one or more additional of Sumanirole or (R)-5,6-dihydro-5-(methylamino)-4H-imi excipients. Preferably the coating composition has a total dazo4.5-ij-quinoline-2(1H)-thione has a core having the solids concentration of about 1% to about 10% by weight, following composition: and a gellan gum concentration of about 1% to about 5% by weight. 0067. Additional excipients present in the coating com active agent 0.1-3% free base equivalent position can include one or more buffering agents, typically lactose monohydrate 50-85% at a concentration of about 0.03% to about 3% by weight; pregelatinized starch 10-45% Xanthan gum O-5% one or more plasticizers, typically at a concentration of flavoring agent O-0.5% about 0.03% to about 3% by weight; and/or one or more water-soluble dye O-0.5% dispersing and/or emulsifying agents, typically at a concen colloidal silicon dioxide 0-1% tration of about 0.03% to about 3% by weight. An example magnesium stearate O.5-5% of a Suitable buffering agent is Sodium citrate. An example of a Suitable plasticizer is propylene glycol. An example of all percentages being by weight. a Suitable dispersing or emulsifying agent is . Fla Voring agents can also be included in the coating composi 0073 Yet another illustrative sublingual tablet of the tion if desired. invention containing as active agent a Salt, e.g., the maleate salt, of Sumanirole or (R)-5,6-dihydro-5-(methylamino)-4H 0068 The coating composition can be prepared by any imidazo4.5-ij-quinoline-2(1H)-thione has a core having Suitable process involving dissolving the gellan gum and the following composition: other, optional, excipients in the vehicle, preferably water. Order of addition is not critical. The water is preferably heated, for example to a temperature of about 55 C. to about 85 C. Gellan gum and other excipients, if present, are added active agent 0.1-3% free base equivalent with Stirring until all ingredients are homogeneously dis microcrystalline cellulose 30-70% pregelatinized starch 25-65% persed. The resulting coating liquid is preferably maintained croscarmellose sodium 0-10% at an elevated temperature during the Stirring and Subsequent Xanthan gum O-5% Spraying procedure. flavoring agent O-0.5% water-soluble dye O-0.5% 0069 Tablet cores to be coated are placed in a suitable colloidal silicon dioxide 0-1% coating apparatus, for example a coating pan, and are magnesium stearate O.5-5% preferably preheated to a bed temperature of about 50 C. to about 70° C. The coating liquid is sprayed on to the tablets all percentages being by weight. under conditions that will be readily optimized by one of skill in the art. Spraying is continued until an amount of EXAMPLES coating Solution equivalent to a weight gain of about 0.1% to about 5% has been applied. The resulting coated tablets 0074 The following examples illustrate aspects of the are preferably cooled to ambient temperature, or about 20 present invention but should not be construed as limitations. C. to about 35 C., prior to discharge from the coating pan. In these examples “compound Z” refers to (R)-5,6-dihydro US 2003/0180357 A1 Sep. 25, 2003

5-(methylamino)-4H-imidazo4.5-ij-quinoline-2(1H)- were homogeneously dispersed. The resulting coating liquid thione, maleate Salt. All percentages are by weight unless having a Solids content of 2.73% was maintained at a otherwise indicated. temperature of 70° C. during the Stirring and Subsequent Example 1 Spraying procedure. 0075) A sublingual tablet formulation was prepared hav 0081 Tablets of Example 1, in an amount of 700 g, were ing the following composition: placed in a 12 inch (approximately 300 mm) coating pan and preheated to a bed temperature of 60° C. The coating liquid was sprayed on to the tablets under the following conditions: compound Z 1.11% Avicel TM PH-101 (microcrystalline cellulose) 46.71% Starch 1500 of Colorcon (pregelatinized starch) 44.00% outlet air temperature 50-60° C. croscarmellose sodium NF 5.00% pan speed 16 rpm colloidal silicon dioxide NF O.50% air flow 30-35 cfm (0.84–0.98 m/minute) cinnamon flavor O.14% atomizing air pressure 10 psi (69 kPa) mint flavor O.04% peristaltic pump setting 15-20 g/minute dye (cherry shade #1632, Crompton & Knowles) O.50% magnesium stearate 2.00% 0082 Spraying was continued until an amount of coating 0.076 Pregelatinized starch and dye were blended in a Solution equivalent to a weight gain of 1.2% had been high-Shear mixer for 2 minutes or until homogeneously applied. The resulting coated tablets were cooled to 30° C. mixed. The following ingredients were then individually prior to discharge from the coating pan. layered over the resulting mixture in the high-Shear mixer: compound Z, microcrystalline cellulose; colloidal Silicon 0083. The tablets had an attractive high gloss appearance dioxide, croScarmelloSe Sodium. Mixing in the high-Shear with cherry red Speckles. mixer was resumed for a further 2 minutes. If the dye was not adequately dispersed throughout the resulting mixture, Example 3 mixing continued in 1 minute increments until good disper Sion of dye was observed. A Small portion of the mixture was 0084. A sublingual tablet formulation was prepared hav then removed and hand-mixed with magnesium Stearate to ing the following composition: form a magnesium Stearate premix. This premix, together with the flavors, was added to the high-Shear mixer and mixed for 1 minute to form a lubricated tablet stock. compound Z 1.05% mannitol, granular 7O.OO% 0077. The lubricated tablet stock was discharged from the sorbitol 16.57% high-Shear mixer and Stored in desiccated hermetically hydroxypropylcellulose, type LH-11 7.00% Sealed containers until ready for tableting. Tablets were Xanthan gum 2.50% prepared by compression using 1%2 inch (approximately 9 colloidal silicon dioxide NF O.50% cinnamon flavor O.14% mm) Plain/Plain tooling with slight curvature to the follow mint flavor O.04% ing Specifications: dye (cherry shade #1632, Crompton & Knowles) O.20% magnesium stearate 2.00%

tablet weight 180 mg hardness 3-4 SCU 0085 Mannitol and dye were blended in a high-shear friability <0.5% mixer for 2 minutes or until homogeneously mixed. The following ingredients were then individually layered over the resulting mixture in the high-Shear mixer: compound Z, Example 2 Sorbitol, hydroxypropylcellulose, Xanthan gum, colloidal 0078 Sublingual tablets prepared as in Example 1 were Silicon dioxide. Mixing in the high-shear mixer was resumed coated with a gellan gum coating according to the following for a further 2 minutes. If the dye was not adequately procedure. dispersed throughout the resulting mixture, mixing contin 0079 A coating liquid having the following composition ued in 1 minute increments until good dispersion of dye was was prepared: observed. A small portion of the mixture was then removed and hand-mixed with magnesium Stearate to form a mag nesium Stearate premix. This premix, together with the flavors, was added to the high-Shear mixer and mixed for 1 gellan gum (Kelcogel TM) 2.00% minute to form a lubricated tablet stock. sodium citrate O.13% propylene glycol O.40% lecithin O.20% 0086 The lubricated tablet stock was discharged from the deionized water 97.27% high-shear mixer and Stored in desiccated hermetically Sealed containers until ready for tableting. Tablets were prepared by compression using 1%2 inch (approximately 9 0080 Deionized water was heated to 70° C. The other mm) Plain/Plain tooling with slight curvature to the follow ingredients were added with Stirring until all ingredients ing Specifications: US 2003/0180357 A1 Sep. 25, 2003

0094 Pregelatinized starch and color were blended in a high-shear mixer for 2 minutes or until homogeneously mixed. The following ingredients were then individually tablet weight 190 mg layered over the resulting mixture in the high-Shear mixer: hardness 3-4 SCU compound Z, microcrystalline cellulose; colloidal Silicon friability <0.5% dioxide, croScarmelloSe Sodium. Mixing in the high-Shear mixer was resumed for a further 2 minutes. If the color was not adequately dispersed throughout the resulting mixture, Example 4 mixing continued in 1 minute increments until good disper sion of color was observed. A small portion of the mixture 0.087 Sublingual tablets prepared as in Example 3 were was then removed and hand-mixed with magnesium Stearate coated with a gellan gum coating according to the following to form a magnesium Stearate premix. This premix, together procedure. with the flavors, was hand screened through a #20 mesh 0088 A coating liquid having the following composition pharmaceutical Screen, then added to the high-Shear mixer was prepared: and mixed for 1 minute to form a lubricated tablet stock. 0095 The lubricated tablet stock was discharged from the high-shear mixer and Stored in desiccated hermetically gellan gum (Kelcogel TM) 2.00% sodium citrate O.13% Sealed containers until ready for tableting. Tablets were propylene glycol O.40% prepared by compression using 1%2 inch (approximately 9 lecithin (Lipoid TM LS-100) O.20% mm) Plain/Plain tooling with slight curvature to the follow flavor O.30% ing Specifications: deionized water 96.97%

tablet weight 180 mg 0089 Deionized water was heated to 70° C. The other hardness 3.5-4 SCU ingredients were added with Stirring until all ingredients friability <0.8% were homogeneously dispersed. The resulting coating liquid having a solids content of 3.03% was maintained at a temperature of 70° C. during the Stirring and Subsequent Example 6 Spraying procedure. 0096 Sublingual tablets prepared as in Example 5 were 0090 Tablets of Example 1, in an amount of 700 g, were coated with a gellan gum coating according to the following placed in a 12 inch (approximately 300 mm) coating pan and procedure. preheated to a bed temperature of 60° C. The coating liquid 0097. A coating liquid having the following composition was sprayed on to the tablets under the following conditions: was prepared:

outlet air temperature 50-60° C. panspeed 16 rpm gellan gum (Kelcogel TM) 2.00% air flow 30-35 cfm (0.84–0.98 m/minute) sodium citrate O.13% atomizing air pressure 10 psi (69 kPa) propylene glycol O.40% peristaltic pump setting 15-20 g/minute lecithin (Lipoid TM LS-100) O.20% hot cinnamon flavor O.30% deionized water 96.97% 0.091 Spraying was continued until an amount of coating Solution equivalent to a weight gain of 1.36% had been 0.098 Deionized water was heated to 70° C. The other applied. The resulting coated tablets were cooled to 30° C. ingredients were added with Stirring until all ingredients prior to discharge from the coating pan. were homogeneously dispersed. The resulting coating liquid 0092. The tablets had an attractive high gloss appearance having a solids content of 3.03% was maintained at a with cherry red Speckles. temperature of 70° C. during the Stirring and Subsequent Spraying procedure. Example 5 0099] Tablets of Example 5, in an amount of 7000 g, were 0093. A sublingual tablet formulation was prepared hav placed in a 24-inch (approximately 600 mm) coating pan and ing the following composition: preheated to a bed temperature of 60° C. The coating liquid was sprayed on to the tablets under the following conditions:

compound Z O.43% Avicel TM PH-101 (microcrystalline cellulose) 47.39% Outlet air temperature 48-55°C. Starch 1500 of Colorcon (pregelatinized starch) 44.00% pan speed 10-14 rpm, preferably 14 rpm croscarmellose sodium NF 5.00% air flow 300-400 efm (8.5-11.3 m/minute) colloidal silicon dioxide NF O.50% atomizing air pressure 20-35 psi (138-242 kPa), cinnamon flavor O.14% preferably about 20 psi mint flavor O.04% peristaltic pump setting 15-40 g/minute?gun (2 gun spray system), color (cherry shade #1632, Crompton & Knowles) O.50% preferably 30-40 g/minute? gun magnesium stearate 2.00% tablet bed temp 37-50° C., preferably about 40°C. US 2003/0180357 A1 Sep. 25, 2003

0100 Spraying was continued until an amount of coating acidifiers, urinary incontinence medications, vasodilators, Solution equivalent to a weight gain of 2.04% had been Vasoprotectants, and combinations thereof. applied. The resulting coated tablets were cooled to 30° C. 5. The tablet of claim 3 wherein the drug is a smoking prior to discharge from the coating pan. cessation drug. 6. The tablet of claim 5 wherein the Smoking cessation 0101 The tablets had an attractive high gloss appearance drug is Selected from bupropion, ibogaine, nicotine and with cherry red Speckles. metabolites thereof. 7. The tablet of claim 3 wherein the drug is an antibac What is claimed is: terial drug. 1. A pharmaceutical tablet comprising a core and a coating 8. The tablet of claim 7 wherein the antibacterial drug is adherent thereto, wherein (a) the core comprises Solid par an oxazolidinone. ticles of a water-soluble dye distributed in a matrix, and (b) 9. The tablet of claim 8 wherein the oxazolidinone is the coating comprises gellan gum. selected from eperezolid, linezolid, N-(5S)-3-3-fluoro-4- 2. The tablet of claim 1 having a Speckled Surface appear 4-(2-fluoroethyl)-3-oxo-1-piperazinylphenyl-2-oxo-5-ox CC. azolidinyl)methyl)acetamide, (S)-N-3-5-(3-pyridyl)th 3. The tablet of claim 1 wherein the core comprises a drug iophen-2-yl)-2-oxo-5-oxazolidinyl)methyl)acetamide, and in a therapeutically and/or prophylactically effective (S)-N-3-5-(4-pyridyl)pyrid-2-yl)-2-oxo-5-oxazolidinyl amount. methyl)acetamide hydrochloride. 4. The tablet of claim 3 wherein the drug is selected from 10. The tablet of claim 3 wherein the drug is an antimi the group consisting of ACE inhibitors, C.-adrenergic ago graine agent. nists, 3-adrenergic agonists, C.-adrenergic blockers, B-adr 11. The tablet of claim 10 wherein the antimigraine agent energic blockers, alcohol deterrents, aldose reductase inhibi is a 5-HT receptor agonist. tors, aldosterone antagonists, amino acids, anabolics, 12. The tablet of claim 11 wherein the 5-HT receptor analgesics (both narcotic and non-narcotic); anesthetics; agonist is Selected from the group consisting of almotriptan, anorexics, antacids, anthelmintics, antiacne agents, anti eletriptan, froVatriptan, naratriptan, rizatriptan, Sumatriptan allergics, antiandrogens, antianginal agents, antianxiety or Zolmitriptan. agents, antiarrythmics, antiasthmatics, antibacterial agents 13. The tablet of claim 3 wherein the drug is useful in and antibiotics, antialopecia and antibaldness agents, anti treating or preventing an ophthalmic disorder. amebics, antibodies, anticholinergic drugs, anticoagulants 14. The tablet of claim 13 wherein the drug is an anti and blood thinners, anticolitis drugs, anticonvulsants, anti glaucoma or intraocular pressure lowering agent. cystitis drugs, antidepressants, antidiabetic agents, antidiar 15. The tablet of claim 14 wherein the antiglaucoma or rheals, antidiuretics, antidotes, antiemetics, antieStrogens, intraocular pressure lowering agent is Selected from the antiflatulents, antifungal agents, antigens, antiglaucoma group consisting of adrenolone, apraclonidine, , agents, antihistaminics, antihyperactives, antihyperlipopro dipivefrin, acebutolol, adaprolol, alprenolol, atenolol, betaX teinemics, antihypertensives, antihyperthyroid agents, anti olol, , bufuralol, bunitrolol, bunolol, bupranolol, hypotensives, antihypothyroid agents, anti-infectives, anti carteolol, carvedilol, cetamolol, deXpropanolol, labetalol, inflammatories (both Steroidal and nonsteroidal); levobunolol, metipranolol, metoprolol, nadolol, nifenalol, antimalarial agents, antimigraine agents, antineoplastics; Oxyprenolol, penbutolol, pindolol, practolol, pronethalol, antiobesity agents, antiparkinsonian agents and antidyski propranolol, Sotalol, timolol, tolamolol, toliprolol, Vani netics, antipneumonia agents, antiprotozoal agents, antipru nolol, acetazolamide, dorZolamide, bimatoprost, latano ritics, antipsoriatics, antipsychotics, antipyretics, antirheu prost, travoprost, unoprostone isopropyl and combinations matics, antisecretory agents, anti-Shock medications, thereof. antispasmodics, antithrombotics, antitumor agents, antituS 16. The tablet of claim 3 wherein the drug is an analgesic, Sives, antiulceratives, antiviral agents, anxiolytics, bacteri antipyretic or anti-inflammatory agent. cidins, bone densifiers, bronchodilators, calcium channel 17. The tablet of claim 16 wherein the analgesic, anti blockers, carbonic anhydrase inhibitors, cardiotonics and pyretic or anti-inflammatory agent is Selected from the group heart Stimulants, chemotherapeutics, choleretics, cholin consisting of aceclofenac, acemetacin, e-acetamidocaproic ergics, chronic fatigue Syndrome medications, CNS Stimu acid, acetaminophen, acetaminoSalol, acetanilide, acetylsali lants, coagulants, contraceptives, cystic fibrosis medica cylic acid, S-adenosylmethionine, alclofenac, alclometa tions, decongestants, diuretics, dopamine receptor agonists, Sone, alfentanil, algestone, allylprodine, alminoprofen, alox dopamine receptor antagonists, enzymes, estrogens, expec iprin, alphaprodine, aluminum bis(acetylsalicylate), torants, gastric hyperactivity medications, glucocorticoids, amcinonide, amfenac, aminochlorthenoxazin, 3-amino-4- hemostatics; HMG CoA reductase inhibitors; hormones; hydroxybutyric acid, 2-amino-4-picoline, aminopropylon, hypnotics, immunomodulators, immunosuppressants, laxa aminopyrine, amiXetrine, ammonium Salicylate, ampiroxi tives, medicaments for oral and periodontal diseases, miot cam, amtolimetinguacil, anilleridine, antipyrine, antrafenine, ics, monoamine oxidase inhibitors, mucolytics, multiple apaZone, beclomethasone, bendaZac, benorylate, benox Sclerosis medications, muscle relaxants, mydriatics, narcotic aprofen, benzpiperylon, benzydamine, , ber antagonists, NMDA receptor antagonists, oligonucleotides, moprofen, betamethasone, beZitramide, C.-bisabolol, bro ophthalmic drugs, oxytocics, peptides, polypeptides and mfenac, p-bromoacetanilide, 5-bromosalicylic acid acetate, proteins; polysaccharides, progestogens, prostaglandins, bromosaligenin, bucetin, bucloxic acid, bucolome, budes protease inhibitors, respiratory Stimulants, Sedatives, Sero onide, bufeXamac, bumadizon, buprenorphine, butacetin, tonin uptake inhibitors, SeX hormones including androgens, butibufen, butophanol, carbamazepine, carbiphene, carpro Smoking cessation drugs, Smooth muscle relaxants, Smooth fen, carSalam, celecoxib, chlorobutanol, chloroprednisone, muscle Stimulants, thrombolytics, tranquilizers, urinary chlorthenoxazin, choline Salicylate, cinchophen, cinmetacin, US 2003/0180357 A1 Sep. 25, 2003

ciramadol, clidanac, clobetasol, clocortolone, clometacin, 18. The tablet of claim 16 wherein the analgesic, anti clonitaZene, clonixin, clopirac, cloprednol, clove, codeine, pyretic or anti-inflammatory agent is a Selective COX-2 codeine methyl bromide, codeine phosphate, codeine Sul inhibitory drug. fate, cortisone, cortivaZol, cropropamide, crotethamide, 19. The tablet of claim 18 wherein the Selective COX-2 deflazacort, desomorphine, desonide, desoximetasone, dex inhibitory drug is a compound having the formula amethasone, deXOXadrol, dextromoramide, dezocine, diam promide, diclofenac, difenamizole, difenpiramide, diflo raSOne, diflucortolone, diflunisal, difluprednate, dihydrocodeine, dihydrocodeinone enol acetate, dihydro n morphine, dihydroxyaluminum acetylsalicylate, dimenoxa O dol, dimepheptanol, dimethylthiambutene, dioxaphetyl Y-N4 4 butyrate, dipipanone, diprocetyl, dipyrone, ditaZol, droxi R15 V cam, emorfaZone, enfenamic acid, enoXolone, epirizole, eptazocine, etersalate, ethenZamide, ethoheptazine, ethoxa Zene, ethylmethylthiambutene, , etodolac, R16 etofenamate, etonitaZene, etoricoxib, eugenol, felbinac, fen bufen, fenclozic acid, fendosal, , fentanyl, fen tiazac, fepradinol, feprazone, , fluazacort, flu where R' is a methyl, amino or imide group, R is cloronide, flufenamic acid, flumethasone, flunisolide, hydrogen or a C- alkyl or alkoxy group, X is N or CR'' flunixin, flunoxaprofen, fluocinolone acetonide, fluocinon where R7 is hydrogen or halogen, and Y and Z are inde ide, fluocortin butyl, fluocortolone, fluoresone, fluo pendently carbon or nitrogen atoms defining adjacent atoms rometholone, fluperolone, flupirtine, fluprednidene, flupred of a five- to six-membered ring that is unsubstituted or nisolone, flu., flurandrenolide, flurbiprofen, Substituted at one or more positions with OXO, halo, methyl formocortal, fosfosal, gentisic acid, , glucametacin, or halomethyl groups. glycol Salicylate, guaiaZulene, halcinonide, halometasone, 20. The tablet of claim 18 wherein the Selective COX-2 haloprednone, hydrocodone, hydrocortamate, hydrocorti inhibitor is Selected from the group consisting of celecoxib, Sone, hydromorphone, hydroxypethidine, ibufenac, ibupro deracoxib, Valdecoxib, parecoxib, rofecoxib, etoricoxib, fen, ibuproxam, imidazole Salicylate, indomethacin, 2-(3,5-difluorophenyl)-3-4-(methylsulfonyl)phenyl)-2-cy indoprofen, isofeZolac, isoladol, isomethadone, isonixin, clopenten-1-one, (S)-6,8-dichloro-2-(trifluoromethyl)-2H isoXepac, isoxicam, ketobemidone, ketoprofen, ketorolac, 1-benzopyran-3-carboxylic acid, 2-(3,4-difluorophenyl)-4- p-lactophenetide, lefetamine, , lofentanil, lona (3-hydroxy-3-methyl-1-butyoxy)-5-4- Zolac, lornoxicam, loxoprofen, lysine acetylsalicylate, (methylsulfonyl)phenyl)-3-(2H)-pyridazinone and salts maZipredone, meclofenamic acid, medrySone, mefenamic thereof. acid, meperidine, meprednisone, meptaZinol, meSalamine, 21. The tablet of claim 3 wherein the drug is an agent metazocine, methadone, methotrimeprazine, methylpred useful in treatment and/or prevention of Sexual dysfunction. nisolone, metiazinic acid, metofoline, metopon, mofebuta Zone, mofeZolac, moraZone, morphine, morphine hydro 22. The tablet of claim 21 wherein the agent is selected chloride, morphine Sulfate, morphoine Salicylate, from the group consisting of PDE5 inhibitors, cyclic AMP myrophine, nabumetone, nalbuphine, 1-naphthyl Salicylate, activators, C.-adrenergic antagonists and dopaminergic ago naproxen, narceline, nefopam, , nifenaZone, nists. niflumic acid, nimeSulide, 5'-nitro-2'-propoxyacetanilide, 23. The tablet of claim 21 wherein the agent is a com norlevorphanol, normethadone, normorphine, norpipanone, pound of formula olsalazine, opium, Oxaceprol, Oxametacine, Oxaprozin, oxy codone, Oxymorphone, oxyphenbutaZone, papaveretum, paramethasone, paranyline, parecoxib, parSalmide, pentaZO cine, periSOXal, , phenadoxone, phenazocine, phenazopyridine hydrochloride, phenocoll, phenoperidine, phenopyrazone, phenyl acetylsalicylate, phenylbutaZone, phenyl Salicylate, phenyramidol, piketoprofen, piminodine, pipebuZone, piperylone, piprofen, piraZolac, piritramide, piroXicam, pranoprofen, prednicarbate, prednisolone, pred nisone, prednival, prednylidene, proglumetacin, prohep tazine, promedol, , propiram, propoxyphene, propyphenaZone, produaZone, protizinic acid, proxazole, ramifenaZone, , rimazolium metilsulfate, rofe or a pharmaceutically acceptable Salt thereof, wherein coxib, Salacetamide, Salicin, Salicylamide, Salicylamide R, R and R are the same or different and are H, C, O-acetic acid, Salicylic acid, Salicylsulfuric acid, Salsalate, alkyl (optionally phenyl Substituted), Cs alkenyl or Salverine, Simetride, Sufentanil, SulfaSalazine, Sulindac, alkynyl or Cso cycloalkyl, or where R is as above and Superoxide dismutase, Suprofen, SuxibuZone, talniflumate, RandR are cyclized with the attached Natom to form tenidap, tenoxicam, terofenamate, tetrandrine, thiazolinob pyrrolidinyl, piperidinyl, morpholinyl, 4-methylpiper utaZone, , tiaramide, tilidine, tinoridine, tiXo aZinyl or imidazolyl groups, cortol, , tolmetin, tramadol, triamcinolone, tropesin, Valdecoxib, Viminol, Xenbucin, Ximoprofen, Zalto X is H, F, Cl, Br, I, OH, C, alkyl or alkoxy, CN, profen and . carboxamide, carboxyl or (C. alkyl)carbonyl, US 2003/0180357 A1 Sep. 25, 2003

A is CH, CH, CHF, CHC1, CHBr, CHI, CHCH, C=O, wherein X is O or S, or a pharmaceutically acceptable Salt C=S, CSCH, C=NH, CNH, CNHCH, CNH thereof. COOCH, CNHCN, SO or N; 25. The tablet of claim 1 that is suitable for peroral B is CH, CH, CHF, CHC1, CHBr, CHI, C=O, N, NH or administration. NCH, and n is 0 or 1; and 26. The tablet of claim 1 that is Suitable for intraoral D is CH, CH, CHF, CHC1, CHBr, CHI, C=O, O, N, NH administration. or NCH. 27. The tablet of claim 1 wherein the coating is present in 24. The tablet of claim 21 wherein the agent is a com an amount representing a weight gain of about 0.1% to about pound of formula 5%. 28. The tablet of claim 1 wherein the gellan gum consti tutes about 25% to 100% by weight of the coating. 29. The tablet of claim 1 wherein the gellan gum consti CH tutes about 50% to 100% by weight of the coating. 30. The tablet of claim 1 wherein the coating further comprises at least one additional excipient Selected from the group consisting of buffering agents, plasticizers and dis N persing and emulsifying agents.