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US 200400.58896A1 (19) (12) Patent Application Publication (10) Pub. No.: US 2004/0058896 A1 Dietrich et al. (43) Pub. Date: Mar. 25, 2004

(54) PHARMACEUTICAL PREPARATION (30) Foreign Application Priority Data COMPRISING AN ACTIVE DISPERSED ON A MATRIX Dec. 7, 2000 (EP)...... OO126847.3 (76) Inventors: Rango Dietrich, Konstanz (DE); Publication Classification Rudolf Linder, Kontanz (DE); Hartmut Ney, Konstanz (DE) (51) Int. Cl." ...... A61K 31156; A61K 31/4439 (52) U.S. Cl...... 514/171; 514/179; 514/338 Correspondence Address: (57) ABSTRACT NATH & ASSOCATES PLLC 1030 FIFTEENTH STREET, N.W. The present invention relates to the field of pharmaceutical SIXTH FLOOR technology and describes a novel advantageous preparation WASHINGTON, DC 20005 (US) for an active ingredient. The novel preparation is Suitable for 9 producing a large number of pharmaceutical dosage forms. (21) Appl. No.: 10/433,398 In the new preparation an active ingredient is present essentially uniformly dispersed in an excipient matrix com (22) PCT Filed: Dec. 6, 2001 posed of one or more excipients Selected from the group of fatty , triglyceride, partial glyceride and (86) PCT No.: PCT/EPO1/14307 eSter. US 2004/0058896 A1 Mar. 25, 2004

PHARMACEUTICAL PREPARATION 0008 Further subject matters are evident from the claims. COMPRISING AN ACTIVE DISPERSED ON A MATRIX 0009. The preparations for the purpose of the invention preferably comprise numerous individual units in which at least one active ingredient particle, preferably a large num TECHNICAL FIELD ber of active ingredient particles, is present in an excipient 0001. The present invention relates to the field of phar matrix composed of the excipients of the invention (also maceutical technology and describes a novel advantageous referred to as active ingredient units hereinafter). The active preparation for an active ingredient. The novel preparation is ingredient is preferably essentially uniformly dispersed, in Suitable for the production of a large number of pharmaceu particular homogeneously dispersed or dissolved, in the tical dosage forms. excipient matrix. A preparation preferably comprises micro Spheres. BACKGROUND ART 0010. The preparations of the invention are distinguished 0002. In order to achieve particular properties of a dosage in particular by high Stability, a release of active ingredient form, Such as, for example, masking in the case of which can be controlled by the particle size and composition active ingredients with an unpleasant taste, resistance to of the matrix, good flow characteristics, good compressibil gastric juice in the case of acid-labile active ingredients or ity and by a uniform delivery of active ingredient. In the case controlled release of an active ingredient, normally active of acid-labile active ingredients it is moreover possible to ingredient pellets are provided with an appropriate func achieve, through choice of the matrix excipients, an acid tional coating. If Such coated pellets are then further pro resistance So that it is possible in the case of oral forms to cessed to dosage forms, for example shaped to tablets by dispense with an acid-resistant coating (enteric coating). In compression with excipients, there is a risk that the coating the case of active ingredients which have an unpleasant taste is damaged and thus the functionality is at least partly lost or, for example, Show a effect in the mouth again. after administration, it has been observed that an unpleasant taste of the active ingredient can be masked, and anesthetic DESCRIPTION OF THE INVENTION effects in the mouth can be avoided, by preparations of the invention. It is particularly worthy of mention that the 0003. It is an object of the present invention to provide a preparations of the invention can be further processed to a preparation for active ingredients which is able to retain a large number of pharmaceutical dosage forms without desired functionality and can be further processed to a large thereby losing a given functionality (Such as taste masking, number of pharmaceutical process forms with negligible resistance to gastric juice, slowing of release). Thus, for impairment of a given functionality. example, on compression of the active ingredient units of the invention no or negligible loSS of functionality is observed 0004. It has now been found, surprisingly, that this object even if deformation of the active ingredient units occurs. In is achieved by a preparation in which an active ingredient is contrast to this, with conventional pellets, which normally essentially uniformly dispersed in an excipient matrix com have a functional coating (Such as taste masking, resistance posed of one or more excipients Selected from the group of to gastric juice, slowing of release), a certain degree of fatty alcohol, triglyceride, partial glyceride and fatty acid damage to the coating and thus to the functionality is eSter. observed on further processing to dosage forms, for example 0005 The invention therefore relates to a preparation in on compression to tablets. This may also in Some cases which an active ingredient is essentially uniformly dispersed to active ingredient being released in an unwanted way. in an excipient matrix composed of one or more excipients 0011. The particle size of the individual units is advan Selected from the group of fatty alcohol, triglyceride, partial tageously less than or equal to 2 mm, preferably 50-800 uM, glyceride and fatty acid ester. particularly preferably 50-700 um and very particularly 0006. It has further been found that particularly advan preferably 50-600 um. Preference is given to microsphers of tageous preparations can be obtained by adding Solid par a particle size of 50-500 um, particularly preferably of affin to the excipient matrix. The invention therefore relates 50-400 lum. Particular preference is given to monomodal further to a preparation in which an active ingredient is microspheres with a particle size of 50-400 um, particularly essentially uniformly dispersed in an excipient matrix com of 50-200 um. posed of at least one Solid paraffin together with one or more 0012 Active ingredients of the invention are, in particu excipients Selected from the group of fatty alcohol, triglyc lar, active pharmaceutical ingredients. Examples of active eride, partial glyceride and fatty acid ester. ingredients which may form part of the preparations of the 0007. The invention further relates to preparations in invention are, in particular, the active pharmaceutical ingre which an active ingredient is essentially uniformly dispersed dients mentioned below: i) in an excipient matrix composed of a mixture comprising 0013 : at least one fatty alcohol and at least one Solid paraffin, ii) in an excipient matrix comprised of a mixture comprising at 0014 ; ; ; least one triglyceride and at least one Solid paraffin, iii) In an ; diplivefrin, ; , espro excipient matrix composed of a mixture comprising at least quin; , hydroxyamphetamine; levonorde one partial glyceride and at least one Solid paraffin or iv) in frin, ; ; ; an excipient matrix composed of a mixture comprising at ; ; ; least one fatty acid ester and at least one Solid paraffin. . US 2004/0058896 A1 Mar. 25, 2004

0015 Adrenocorticosteroids: levomethadyl hydrochloride; levonantradol; , lofemizole, lofentanil oxalate; lorcina 0016 ; desoxycorticosterone acetate; dol, lomoxicarn; Salicylate, mefenamic deSoxycorticosterone pivalate; add; menabitan; meperidine, meptaZinol, metha acetate; acetate; , hydro done; methadyl acetate; methopholine; methotrime hemisuccinate, prazine, metkephamid acetate, mimbane, mirfenta hemisuccinate, , ; nil; molinaZone; Sulfate; ; acetate; . nabitan; nalbuphine, nalmeXOne, namoxyrate; nant 0017 Agents to prevent alcohol abuse: radol, naproxen; naproxen; naproXol; ; neX eridine, noracy methadol; ocfentanil; octaZamide, 0018 , acamprosate, , fome olvanil; ; oxycodone; oxycodone; oxyc pizole, , nadide, nitrefazole, . odone terephthalate; oxymorphone, pemedolac, pen 0019 antagonists: tamorphone; ; pentazocine; phenaZopy ridine, phenyramidol; picenadol; pinadoline; 0020 canrenoate; can renone, ; meXrenoate, prorenoate, , epoStane, pirfenidone, piroXicam olamine, pravadoline; prodi meSpire none; OXprenoate, , , lidine, profadol; propiram; propoxyphene, pro , . poxyphene napsilate; proxazole, proXorphan; pyrro liphene, remifentanil; Salcolex, Salethamide maleate; 0021 Amino acids: Salicylamide, Salicylate meglumine; Salsalate, Sali cylate; Spiradoline, Sufentanil; Sufentanil; talmeta 0022 ; ; ; , iso cin; talniflumate; taloSalate; taZadolene; tebufelone; leucine; leucine; ; ; ; tetrydamine; tifurac, tilidine, tiopinac, tonazocine; , ; threonine, ; ; ; trefentanil; trolamine; Veradoline, Verilo Valine. pam; volazocine, Xorphanol, , Zenazocine 0023 Active ingredients for ammonium detoxifica mesilate, Zomepirac, Sucapsaicin. tion: 0031) : 0024 arginine, arginine glutamate, arginine hydro chloride; ; 0032 ; ; ; , ; methylt 0025) Anabolics: estosterone; decanoate; nandrolone 0026 androstanolone, diproplonate; phenpropionate, ; ; oxymester ; undecylenate; ; bol one; ; ; ; Silan nantalate; ; acetate; drone, , ; testosterone cypi , ; mesteronole, met Onate, ; teStoSterOne andienone; nandrolone, Oxandrolone, prasterone; ketolaurate, testosterone phenylacetate, testosterone Stanozolone, ; , ; propionate, . nandrolone cyclotate, norbolethone, ; 0033) Anesthetic additives: acetate; , . 0034) sodium oxibate. 0027 Analeptics: 0028 ; ; endomide; ; 0035 Anesthetics (non-inhalation): fenoxypropazine; ; hexapradol; niala 0036) ; amolanone; ; ; mide, nicethamide. ; levoxadrol; ; ; , , ; ; 0029 : pramoxine, ; remifentanyl; Sufentanyl; tile 0030 acetaminophen; alfentanil; aminobenzoate; tamine; . aminobenzoate; anidoxime; anileridine, anilleridine, anilopam; anirolac, antipyrine; ; benoxapro 0037 Anesthetics (local): fen; ; hydrochloride; brifen 0038 ambucaine; amoxecaine; ; tanil; brom adoline; bromfenac, ; aptocaine; ; benoXinate, benzyl alcohol, butacetn; butixirate; ; butorphanol, car ; betoxycaine; biphenamine; bucricaine; bamazepine, carbaspirin ; carbiphene; bumecaine, ; ; ; buta carfentanil; ciprefadol Succinate, ciramadol, cirama nilicaine; carbizocaine; clibucaine; dol; clonixeril; clonixin; , codeine phos clodacaine, ; dexivacaine, diamocaine; phate, codeine Sulfate; conorphone, ; dibucaine, dyclonine; elucaine; , euprocin, ; dexpemedolac, ; diflunisal; feXicaine, fomocaine; heptacaine; ; , dimefadane, dipyrone, doxpicom hydroxyprocaine; hydroxytetracaine, isobutamben; ine, drinidene, enadoline, epirizole; ergo tamine tar ; leucinocaine; lidocalne, ; trate; ethoxazene, etofenamate, ; fenoprofen; ; octocalne, , oxethacaine; fenoprofen calcium; fentanyl citrate; floctafenine; Oxybuprocaine, parabutoxycalne, phenacaine; pinol flufenisal; flunixin; flunixin meglumine; ; caine, , ; polidocanol, flu.proquaZone; fluradoline; flurbiprofen, hydromor pramocaine; ; ; propanocaine; phone, ibufenac; indoprofen, ketazocine, ketorfanol; propipocaine; ; , pyr ketorolac, letimide, levomethadyl acetate; rocaine, quatacaine, quinisocaine, ; US 2004/0058896 A1 Mar. 25, 2004

rodocaine; , Salicyl alcohol; Suicaine, tet hoquizil; imOXiterol, ipragratine, ipratroplum bro racaine; trapencaine, . mide, isoetharine, isoproterenol; ; , meduitamium iodide, metaproterenol; 0039. Appetite suppressants: meXafylline; nardeterol; nestifylline, nisbuterol; 0040 ; amfetamine; , amfe picumeterol, piquizil; , , reprot cloral, anisacril; benzfetamine, ; erol, RO-24-4736, quaZodine, quinterenol; racepi , ; , ; nephrine, , , , Salme deXamfetamine; , difemetorex, efil terol, Saimeterol Xinafoate, Sevitropium mesilate; amfetamine, etolorex, , fencamfamiln; Soterenol; Sulfonterol; Suloxifen, TA-2005; theo ; , , fluidorex, flu phylline; ; ; minorex, formetorex; , imanixil; indan tiaramide; tipetropium , , orex, levamfetamine; levofacetoperane, leVofenflu , Zindotrine; . ramine; levopropylhexedrine, , , , , norpseudoephedrine; 0047 Beta-blockers: ; ; , , phen 004.8 acebunolol; ; ; ; dimetrazine; ; , , alprenoXime, , , , , Satietine, SetaZindol, ; triflorex, trifluo ; benzodioxine; , ; CX. ; bormetolol; ; bomaprolol; bre fonalol; ; ; buftiralol; ; 0041) : bunolol, , ; ; buro 0042 ; ; albendazole oxide; crolol, , , , ; amidantel; amoScanate, antafenite, antazonite, , , , , clo anthelmycin; antholimine; bephenium hydroxynaph ranolol, , , deXpropra thoate; bidimazium iodide; bisbendazole; bithion nolol, , dichlorisoproterenol; dilevalol; oloxide; bitOScanate, bromoxanide; brotianide; , dropranolol, , , eri bunamidine, butamisole; butonate, cambendazole; colol; eSatenolol, ; , fallintolol, fies carbantel, cidobendazole; clioxanide; cloSantel; dex tolol; ; hydroxycarteolol; hydroxyterta amisole; diamfenetide; , diethylcarbam tolol ; ICI-118551; ; ; azine, dimantine, diphenan; ; dribenda , ; isamoltan; , landi Zole, eprinomecUn; ; etibendazole; olol; ; ; levocicloprolol; febantel; ; ; flurantel; fta , , mephenoxalone; mepin lofyne; furodazole; haloxon; hexylresorcinol; imcar dolol, metalol, , , mind bofos; ; ; ; metri Odilon; ; ; , nafetolol, fonate; metyridine, ; ; napitane, , neraminol; , ; naftalofoS, netobimin, niclofolan; , nit oberadillol, Oxanamide, , pacrinolol, ramisole, nitrodan; , nitroXinil; oltipraz, , , , parodilol; penb ontlanil, , ; oxyclo utolol; penirolol; PHQA-33; ; pirepolol; Zanide; parbendazole, peXantel; piperamide, pipera ; prenalterol; , , pron Zine adipate, calcium edetate, piperamide etalol; propacetamol, , ; ; proclonol; pamoate, pyrantel , ronactolol, ; ; TA-2005; tartrate, pamoate, rafoxanide; resorantel; , , teoprolol, , terthianolol, Salantel; Spirazine, Stilbanzium iodide, Subendazole; , ; , , , tetramisole; thenium closilate; thiofuradene, tia , tribendilol, trigeVolol, ; bendazole, ticarbodine, tioxidazole, ; , Y-12541; ZAM1-1305. triclofenol piperazine, uredofos, VincofoS, Zilantel. 0049 : 0043 therapeutics: 0050 betanidine; tosilate; cromanidine; 0044) adapalene; adelmidrol; benzoyl peroxide; ; ethomoxane, guabenXan; , betacarotene, , , ; guanacline, , , guancidine, doretinel, Salnacedin, etretinate; guanclofine, , , guaniSo fumaric acid; halofuginonen; acetate; quine, , guanoctine, , guan isotretinoin, linolenic acid; ; masoprocol; OXan; guanoxyfen; olmidine, ; pyroxami , motretinide; namiroteine; rosterellone; dine, Solypertine, Spirgetine. Sumaroteine, tazarotene; tematotene, tioxolone; ; tradecamide, tretinoin, triadimenol; 0051 Alpha 1 antagonists: ; Zeranol, Zimidoben. 0052 ; adozelesin; ; ; ; ; CI-926; DL017; dapipra 0045 : Zole; mesilate, ; 0046) ; azaspirium chloride; ; euigenodilol; ; GI-231818; GYKI-12743; ; bitoiterol; ; butaprost; car GYKI-16084, indoramine; ; MK-912; buterol, cipamfylline; , doxaprost, doxofyl , , ; neSapidil; nicer line, dyphylline, ; ephedrine, ; goline; ; peradoxime; peraquinsine; per etanterol, fenspiride; flutropium bromide, formot aUZole, perbufylline, phendioxan, phenoxyben erol, guaithylline; , Hoku-81; Zamine, , podilfen, ; US 2004/0058896 A1 Mar. 25, 2004

; RS-97078; proroxane; ; SGB ole, ketoufen, L-648051; levcromakalim; lodoxam 1534, SL-89.0591; ; ; ; ide ethyl, lodoxamide tromethamine; , tibalosin, ; ; ; upid oXarbazole, piriprost, , pobilukast, pran oSin; ; ; . lukast, ritolukast, Sulukast, tiaramide, Ubenelast; tomelukast, Verlukast, Verofylline; , Zileu 0.053 ACE inhibitors: tOn. 0054) alacepril; benazepril; benazeprilat; BMS-189921; BRL-36378; captopril; ceronapril; 0061. Other antiallergics (for example leukotriene CGS-13928C; cilazapril; cilazaprilat; dehydrocapto antagonists): pril; delapril; enalapril; enalaprilat; EU4867; EXP 0062 acitazanolast; , alinastine; altoqua 7711; fasidotril; fosinopril; fosinoprilat; idrapril; line; , andolast, , ataquimast; imidapril, imidaprilat, indolapril; libenzapril; lisino ; , ; barmastine, batebu pril; mixanpril; moexipril; moexiprilat, moveltipril; last; BAY-X-1005; BAY-X-7195; bepiastine; bepo omapatrilat, orbutopril, pentopril; perindopril, per tastine; BIIL-284, bilastine; binizolast; ; indoprilat, pivopril, quinapril, quinaprilat, ramipril; bunaprolast, cabastine, carebastine, ; rentiapril; Sampatrilat; SCH-54470; spirapril; spira CI-959; ; ; CMI-977; cro prilat, temocapril; temocaprilat; teprotide; trandola mogleic acid, cromolyn natrium; dametralast, deslo pril; trandolaprilat; utibapril; utibaprilat, Z-13752A; ratadine, dlmenhydrinate; ; Zabicipril, Zofenopril; Zofenoprilat. doqualast; dorastine, E-4704, efietirizine, emedas tine, enofelast; enoXamast, , eclaZolast; epi 0055 Renin antagonists nastine; ; flezelastine; HSR-609, KCA 0056) CGP-38560; ciprokiren; CP-108671; 757; ; ; linetastine; enalkiren; ES-6864, FK-906; remikiren; terlakiren; , LY-293111; mapinastine, meduitamium Zankiren. iodide, meduitazin; minocromil, ; MK-886; ; moxilubant, , 0057 Antiallergics such as PDE inhibitors: nedocromil calcium; nedocromil Sodium; nivime 0.058 ; , AWD-12-281 (N-(3,5- done; noberastine; norastemizole; octastine, ONO dichloro-4-pyridinyl)-2-1-(4-fluorobenzyl)-5-hy 4057; OntaZolast, , , pentiget droxy-1H-indol-3-yl)-2-oxoacetamide); BAY-19 ide; perastine, piclopastine, picumast, pirquinozol, 8004 (ethaneSulfonic acid 2-(2,4- poisonoak extract; probicromil, proXicromil, quaZo dichlorophenylcarbonyl)-3-ureidobenzofuran-6-yl last, , quinotolast, raxofelast; repirinast; ester); benafentrine; CC-1088; CDC-801 (B-3-(cy REV-5901-A, rocastine; ; SKF-S-106203; clopentyloxy)4-methoxyphenyl-1,3-dihydro-1,3-di Sequifenadine, , SudeXanox, tagorizine; OXO-2H-isoindole-2-propanamide); CDC-998; ; taZanolast, tazifylline; temelastine; terfena CI-1018; (cis-4-cyano-4-(3-cyclopenty dine, tetraZolast; texacromil; thiazinamium chloride; loxy-4-methoxyphenyl)cyclohexane-1-carboxylic tiacrilast; tiprinast meglumine; tiXanox, tranilast; acid); ; cipamfylline (8-amino-1,3-bis(cy WY-50295; ZD-3523; Zepastine. clopropylmethyl)); D-4396; D-4418 N-(2, 5-dichloro-3-pyridinyl)-8-methoxy-5-quinolinecar 0063 Amebicides: boxamide; darbufelone; denbufylline; ER-21355; 0064. 1B-bisamidine; berythromycin; bialamicol; ; ; IC-485; indolidan; laprafylline; carbarSone; ; chloroquine, clamoxyquin; lixazinone; MESOPRAM (-)-(R)-5-(4-methoxy-3- ciloquinol, dehydroemetine; difetarSone; diloxanide; propoxyphenyl)-5-methyloxazolidin-2-one; emetine, etofamide; iodoquinol, lachnumon; lirol nitraduaZone; NM-702; ; ORG-20241 dine, paromomycin Sulfate; pinafide; quinfamide, (4-(3,4-dimethoxyphenyl)-N2-hydroxythiazole-2- Satranidazole, Stevaladil; Stirimazole, Symetine; carboxamidine); , pumafentrine ((-)-cis teclozan, ; tilbroqulnol; 9-ethoxy-8-methoxy-2-methyl-1,2,3,4,4a,10 Ob-hexahydro-6-(4-diisopropylaminocarbonylphe 0065 : nyl)benzoc1,6-naphthyridine); ; 0066 abiraterone; , cioteronel; cyprot RO-15-2041; (3-(cyclopropylmethoxy)- erone, delanterone, ; droSpire none, epi N-(3,5-dichloro-pyridyl)-4-(difluoromethoxy)-ben tioStanol; inocoterone, L-654066; minameStane, Zamide); ; SCH-351591; SH-636; tibenelast , , ; ; (5,6-diethoxybenzobthiophene-2-carboxylic acid); rosterellone; topterone; . tolafentrine; ; V-11294A (3-3-(cyclopen tyloxy)-4-methoxyphenyl)methyl-N-ethyl-8-(1-me 0067 Antianemics: thylethyl)-3H-purin-6-amine); YM-58997 (4-(3-bro 0068 ancestim; diciferron; epoetin alfa, epoetin mophenyl)-1-ethyl-7-methyl-1,8-naphthyridin beta; epoetin epsilon; epoetin gamma; epoetin 2(1H)-one); YM-976 (4-(3-chlorophenyl)-1,7- omega; ferrous Sulfate, FK-352, folic acid; gleptof diethylpyrido 2,3-dipyrimidin-2(1H)-one); erron; monoisopropyl ester; leucovorin . calcium; tucaresol; TYB-5220; velaresol; 0059) Other antiallergics for treatment: 0069. : 0060 ablukast; atreleuton; bunaprolast; cinalukast; 0070 alinidine; ; besylate; cromitrile; cromolyn; FPL-55712; iralukast; isamox- amlodipine maleate, azaclorzine; bamidipine, ber US 2004/0058896 A1 Mar. 25, 2004

tosamil; betaxolol, bertosamil, bevantolol; Sodium; ceftriaxone Sodium; cefuroxime; ; butoprozine; carvedilol; CD832; cefuroxime axetil, cefuroxime pivoxetil, cefuroxime CERM-11956; maleate; crobenetine; Sodium; cephacetrile Sodium; cephalexin; cephal cyclovirubuxine-D, desocriptine, ; exin; cephaloglycin; ; cephalothin dopropidil; elgodipine; EMD-57283; eniporide; Sodium; cephapirin Sodium; cephradine, cetocycline; ethacizine; ; FK-409; , floSaudil; cetophenicol; chloramphenicol, chloramphenicol floseduinan; FR-46171; GP-1-468; GP-1-531; palmitate, chloramphenicol pantothenate complex; hyperin, ipramidil, isosorbide dinitrate; ivabradine, chloramphenicol Sodium Succinate, chlorhexidine KC-764; KRN-2391; KW-3635; ligustizine; linsi phosphanilate; chloroxylenol; chlortetracycline domine; metoprolol Succinate; ; mildr bisulfate; chlortetracycline, cinoxacin; ciprofloxa onate, ; molsidomine, monatepil maleate; nafagrel; NK-341; OP-2000; pirsidomine; pivazide; cin; ; cirolemycin; ; ; primidolol; ; SL-87.0495; clinafloxacin, ; clindamycin; clindamy ST-1324, tedisamil, toSifen, Vatanidipine, ; cin palmitate; clindamycin phosphate; clofazimine; cloxacillin benzathine, cloxacillin Sodium; clox Y-27152; Zatebradine. yguin; colistimethate Sodium; colistin Sulfate; 0071 : coumermycin; coumermycin Sodium, cyclacillin; ; dalfopristin, dapsone, daptomycin; 0072 ; ; mesilate; , demeclocycline, demecycline; ; ; , mirisetron denofungin; diaveridine, ; dicloxacillin maleate; , ; , pan Sodium, dihydroStreptomycin Sulfate; dipyrithione; copride; , , cit dirithromycin, doxycycline, doxycycline calcium; rate; . doxycycline foSfatex, doxycydine hyclate; droxacin 0073 Antiarthritics: Sodium; enoxacin; epicillin; epitetracycline, erythro mycin; erythromycin acistrate, erythromycin esto 0074 AI-200; auranofin; , cipemas late, erythromycin ethylSuccinate, erythromycin glu tat; etanercept; etebenecid; interleukin-6, lefluno ceptate, erythromycin lactoblonate, erythromycin mide; lenercept; lobenzarit; lodelaben: M-5010; propionate, erythromycin Stearate; ethambutol; parecoxib; rofecoxib; RS-130830; S-2474; ethionamide, fleroxacin; floxacillin; fludalanine; TSA-234, valdecoxib; flumequine; fosfomycin; fosfomycin tromethamine; 0075 Antiatherosclerotics: fumoxicillin; furazolium chloride; furazolium tar trate; fusidate Sodium; fusidic acid; gentamicin Sul 0076) H-327/86; mifobate; lodaZecar; riboflavin fate, gloximonam, gramicidin; ; hetacil butyrate; timefurone. lin; ; hexedine; ibafloxacin, ; isoconazole, isepamicin; ; joSamycin; kana 0.077 Bacteriostatics: mycin Sulfate; kitasamycin; levofuraltadone; levo 0078 acedapsone; acetosulfone sodium; alamecin; propylcillin, lexithromycin; lincomycin; lincomycin; alexidine, amdinocillin, amdlnocillin pivoxil, ami lomefloxacin, lomefloxacin, lomefloxacin mesilate; cycline, amifloxacin; amifloxacin mesilate; amika loracarbef, mafenide; meclocycline; meclocycline cin; amikacin Sulfate, aminosalicyllic acid; ami Sulfosalicylate; megalomicin phosphate; medulidox; noSalicylate Sodium; ; amphomycin; meropenem; methacycline, methacycline; meth ampicillin; amplicillin Sodium; apaicillin Sodium; enamine, methenamine hippurate; methenamine apramycin; aspartocin, astromicin Sulfate; avilamy mandelate; methicillin Sodium; metioprim; metron cin, avoparcin, azithromycin; aziocillin; aziocillin idazole; phosphate, meZiocillin; Sodium; bacampicillin hydrochloride; bacitracin; meZiocillin Sodium; , minocycline, mir bacitracin methylene disalicylate; bacitracin , incamycin; monensin; monensin Sodium, nafcilin bambermycins, benzoylpas calcium; berythromycin; Sodium; nalidixate Sodium; nalidixic acid; natainy betamicin Sulfate; biapenem; biniramycin; biphe cin, nebramycin; palmitate, neomycin Sul namine hydrochloride; bispyrithione magSulfeX; fate, neomycin undecylenate, netilmicin Sulfate; butikacin; butirosin Sulfate; capreomycin Sulfate; neutramycin; nifuiradene, nifuraldeZone, nifuratel; carbadox, carbenicillin disodium; carbenicillin inda nifuratrone, nifurdazil; niftrimide, niflupirinol, nyl Sodium; carbenicillin phenyl Sodium; carbenicil nifurcquinazol; nifurthiazole, nitrocycline, nitro lin; carumonam Sodium, cefaclor, cefadroxil, cefa furantoin, nitromlde; norfloxacin; novobiocin mandole, cefamandole nafate, cefamandole Sodium; Sodium; ; onnetoprim; oxacillin Sodium; cefaparole, cefatrizine, cefazaflur Sodium, cefazolin; oXimonam, OXimonam Sodium; ; cefazolin Sodium, cefbuperaZone, cefdinir, Oxytetracycline; oxytetracycline calcium; oxytetra cefepime, cefepime, cefetecol, cefixime, cef cycline, paldimycin; parachlorophenol; paulomycin; menoXime, cefimetazole, cefmetazole Sodium; pefloxacin; pefloxacin mesilate; penamecillin; peni cefonicid monosodium, cefonicid Sodium, cefopera cillin G benzathine; G, penicillin G Zone Sodium, ceforanide, cefotaXime Sodium; procaine; penicillin G Sodium; penicillin V, penicil cefotetan, cefotetan disodium, cefotiam, cefoxitin; lin V benzathine; penicillin V hydrabamine; penicil cefoxitin Sodium, cefpimizole, cefpimizole Sodium; lin V; pentizidone Sodium; phenyl aminoSalicylate; cefpiramide, cefpiramide Sodium, cefpirome Sulfate; piperacillin Sodium, pirbenicillin Sodium, piridicillin cefpodoxime proxetil, cefprozil, cefroXadine, cefSu Sodium, pirlimycin; pivampicillin, pivampicillin lodin Sodium, ceftazidime, ceftibuten, ceftizoxime pamoate, pivampicillin probenate; polymyxin B Sul US 2004/0058896 A1 Mar. 25, 2004

fate; porfiromycin; propikacin; pyrazinamide, Sodium; , , , flu pyrithione Zinc, quindecamine acetate; quinupristin; razepam, flu Zinamide; Sodium; gabap racephenicol; ramoplanin; ranimycin; relomycin; entin, ilepcimide, , magnesium Sulfate; repromicin; rifabutin, rifametane, rifamexil; rifa , mephobarbital; methetoin, methSux mide, rifampin; rifapentine, ; rollitetracy imide, millacemide, nabaZenil, nafimidone; cline, rollitetracycline nitrate; rosaramicin; rosarami , ; ; phenobar cin butyrate; rosaramicin propionate, rosaramicin bital Sodium; , , phenytoin Sodium phosphate, rosaramicin Stearate; roSoxacin; Sodium; ; , ralitoline, remace roXarSone; ; Sancycline, Sanfeltrinem mide; ropizine, , , Sulthiame; Sodium; Sarmoxicillin; Sarpicillin; Scopafungin; Siso thiopental Sodium; ; , tri micin; Sisomicin Sulfate, Sparfloxacin; Spectinomy methadione; Sodium; Valproic acid; cin; Spiramycin; Stallimycin; Steffimycin; Streptomy ; ZonicleZole; . cin Sulfate; StreptonicOZid; Sulfabenz, Sulfabenzamide, Sulfacetamide, Sulfacetamide 0085 : Sodium, Sulfacytine, Sulfadiazine, Sulfadiazine 0086 adatanserin; ; adinazolam mesi Sodium, Sulfadoxine, Sulfalene, Sulfamerazine, Sul late, ; aletamine; ; ; fameter, Sulfamethazine, Sulfamethizole, Sul , maleate, azaloxan fumarate; famethoxazole, Sulfamonomethoxine, Sulfamoxole; , ; bipenamol, ; Sulfanilate Zinc, Sulfanitran; SulfaSalazine, Sulfa butacetin, , ; ; Somizole, Sulfathiazole, Sulfazamet, Sulfisoxazole; , ; mesilate; cloda Sulfisoxazole acetyl, Sulfisboxazole diolamine, Sul Zon; ; fumarate, cyclindole; fomyxin; Sulopenem; Sultarmicillin; Suncillin , cyprolidol, cyproximide; Sodium; talampicillin, telcoplanin; temafloxacin; tosylate, , daZadrol maleate, dazepinil; temocillin, tetracycline, tetracycline, tetracycline ; dexamisole; deximafen; ; phosphate complex, tetroXoprim; ; dioxadrol; dothiepin, ; dulloxetine, eclan thiphencillin, ticarcillin cresyl Sodium, ticarcillin amine maleate, encyprate, ; fantridone; disodium, ticarcillin monosodium, ticlatone, tiodo fehmetoZole; femmetramide, fumarate; nium chloride; tobramycin; tobramycin Sulfate, toSu ; ; fluoxetine, , gam floxacin; trimethoprim; trimethoprim Sulfate; trisul feXine, guanoxyfen Sulfate; imafen, , imi fapyrimidines, ; trospectomycin pramine; , ; lprindole, iso Sulfate; tyrothricin; Vancomycin; Vancomycin; Vir carboxazid; ketipramine fumarate; ; giniamycin; Zorbamycin. lortalamine; , maprotiline; ; 0079 : millacemide; ; , , modaline Sulfate, napacitadine, napamezole; nefaz 0080 alverine citrate; anisotropine methylbromide; odone; , nitrafudam; maleate; ; atropine oxide; atropine Sulfate; bella ; phosphate, ; donna; benapry Zine; benzetimide, benzilonium bro ; ; ; pheneizine Sul mide; ; biperiden; biperiden lactate; clid fate, , pizotyline; ; , inium bromide, cyclopentolate, deXetimide, , maleate; rolicyprine; dicyclomine, dihexyverine, domazoline fumarate; , , Sibutramine, , Suri elantrine; elucaine; ethybenztropine, eucatropine; toZole; ; fumarate; tan glycopyrrolate; heteronium bromide; homatropine damine; thiaZeSim, ; tomoxetine; traZ hydrobromide; homatropine methylbromide; hyos odone; trebenzomine; , trimipramine cyamine, hydrobromide, hyoscyamine maleate; , ; Zimeldine, Sulfate, isopropamide iodide, mepenZolate bromide, Zometapine. methylatropine nitrate; metoquizine; chloride; parapenzolate bromide, pentapiperium 0087 Antidiabetics: methylsulfate; phencarbamide, poldine methylsul 0088 ; bimoclomol; BM-17.0249; fate; proglumide, propantheline bromide, propen ; butoxamine, , centpiperalone; Zolate, hydrobromide; tematroplum ; clomoxir; etoformin, ; methylsulfate; tiquinamide, ; toguizine, tri fenbutamide; GI-262.570; gliamilide; ; ampyZine Sulfate; trihexyphenidyl, tropicamide. , glibutimine; , glicetanile 0081 : Sodium; , glicondamide, glidaZamide, gliflumide, ; glipalamide, , 0082) ancrod; ardeparin sodium; bivalirudin; bro , glisamuride, glisentide, glisindamide, mindione; dalteparin Sodium; desirudin; dicumnarol; glisolamide, ; glucagon, glyburide; gly calcium; heparin Sodium; lyapolate Sodium; buthiazol, glybuzole, , glycycla nafamoStat mesilate; , tinzaparin mide; glyhexamide, glymidine Sodium; glyocta Sodium; Sodium. mide; glyparamide, glypinamide; glyprothiazol; glysobuzole; heptolamide; HMR-1964; ; 0083) : insulin argine; ; insulin dalanat; insulin 0084 ; ameltolide; atolide; buramate; car defalan; , ; insulin bamazepine, cinromide, citenamide; , human; insulin human, isophane; insulin human cyheptamide, dezinamide; dimethadione; divalproex Zinc, insulin human Zinc, extended; insulin, US 2004/0058896 A1 Mar. 25, 2004

isophane; ; insulin, neutral; insulin Zinc, nitrate, calcium undecylenate; candicidin; carbol insulin Zinc, extended; insulin Zinc, isaglidole; JTT fuchsin, chlordantoin, ciclopiroX, ciclopiroX ola 501; JTT-608; mebenformin; ; metfo mine; cillofungin; cisconazole; ; min, methyl palmoxirate; , midaglizole; cuprimyxin; denofungin; dipyrithione, doconazole; ; ; NN-304; NVP-DPP-728; econazole; econazole nitrate, enilconazole; ethonam palmoxirate sodium; PNU-106817; ; pro nitrate; fenticonazole nitrate; filipin, fluconazole; insulin human; Seglitide acetate; tibeglisene, flucytosine, fungimycin; , hamycin; iso tiformin; , , tolpyrramide; conazole, , kalafungin; ; lomofimgin; lydimycin; mepartricin; ; 0089 Aldose reductase inhibitors: miconazole nitrate; monensin; monensin Sodium; 0090 AD-5467; alrestatin; ; dargilita naftifine; neomycin undecylenate, nifuratel; nifur Zone, Sodium, , ; imi merone, nitralamine, nyStatin; octanoic acid; orcona restat; linogliride; linogliride; MCC-555; minalr Zole nitrate; oxiconazole nitrate; oxifungin; parcona estat; NZ-314, , pirogliride, ponalrestat; Zole, partricin; iodide, proclonol; pyrithione Zinc, ; risarestat; ; tendamistat, tolr pyrrolnitrin; rutamycin; Sanguinarium chloride; estat; ; ; Zopolrestat. Saperconazole, Scopafungin; Sulfide, Sine fungin; Sulconazole nitrate; terbinafine; ; 0091 Alpha-glucosidase inhibitors: thiram, ticlatone, tioconazole, tolciclate; tolindate; 0092 , camiglibose, emiglitate; englita , triacetin; triafungin; ; Zone; ; moranoline; . Viridofulvin, Zinc undecylenate, Zinoconazole. 0093 Antidiarrheals: 0109 : 0094) rolgamidine, diphenoxylate (Lomotil), met 0110 alprenoxime; ; dapiprazole; dipiv ronidazole (Flagyl), methylprednisolone (Medrol), efrin, naboctate; pilocarpine, pimabine. SulfaSalazine (AZulfidine). 0111 : 0.095 Antidiuretics: 0112 acrivastine; phosphate; astemizole; 0096) argipressin tannate; desmopressin acetate; aZatadine maleate, barmastine, bromodiphenhy lypressin. dramine; brompheniramnine maleate; carbinoxam ine maleate, cebrizine, chlorpheniramine maleate; 0097 : chlorpheniramine polistirex, ; clemastine; 0098 ; edrophonium chloride; fomepi clemastine fumarate; closiramine aceturate, cyc Zole; leucovorin calcium; levoleucoVorin calcium; liramine maleate, , , dexbro ; Sulfate. mpheniramnine maleate; maleate; dimethindene maleate, diphenhydramine 0099 : citrate; diphenhydramnine; dorastine, 0100 ; ; ; ben Succinate, ebastine; levocabastine, loratadine, Zquinamide; , chlorpromazine; ; noberastine; citrate; , cyclizine; , diphenidol; pyrabrom, pyrilamine maleate, pyroxamnine male diphenidol; diphenidol pamoate, meSi ate, rocastine; rotoxamine; taZifylline; temelastine, late, ; dronabinol, , flumeri , citrate, tripelennamine; done; galdansetron; ; granisetron, luro ; Zolamine. Setron mesilate; , , , ondansetron; pancopride; prochlor 0113 Lipid-lowering agents: , edisylate; prochlorpera 0114 cholestyramine resin; ; ; Zine maleate; ; ; thieth crilvastatin; dalvastatin; Sodium; ylperazine malate; thiethylperazine maleate; Sodium; ; lecimibide, lovasta , . tin, ; Sodium; , Simvasta 0101 Antiepileptics: tin, tiqueside; Xenbucin; acifran; beloxamide, beZafi brate; boxidine, butoxamine, cetaben Sodium; 0102) ; ; . , gemcadiol; halofenate; ifibrate; meglu tol, nafenopin; pimetine; theofibrate; tibric acid; tre 0103) (non-steroidal): loXinate. 0.104) clometherone; ; nafoxi dine, citrate, , cit 0115) Antihypertensives: rate, citrate, mesilate. 0116 alfuzosin; alipamide; althiazide, amiquinsin; 0105 Antifibrinolytics: amlodipine beSylate; amlodipine maleate; anaritide acetate, maleate; belfoSdil, bemitradine, 0106 camostat; nafamostat mesilate. bendacalol mesilate; ; benzthi azide, betaxolol; Sulfate; bevantolol; 0107 Fungistatics: biclodil; bisoprolol; bisoprolol fumarate; ; 0.108 acrisorcin; ambruticin; amphotericin B; aza , buthiazide: candoxatril; candoxatrilat; conazole, azaserine, basifungin; bifonazole; biphe captopril; carvedilol, ceronapril; namine; bispyrithione magSulfeX; butoconazole Sodium; ; cilaZapril; , clonidine, US 2004/0058896 A1 Mar. 25, 2004

, , , dar acetate; isoxepac, isoxicam, ketoprofen; lofemizole; odipine, debrisoquin Sulfate; delapril; diapamide, lomoxicam, lonazolac, etabonate; ; dilevalol, malate; ditekiren; meclofenamate Sodium; ; meclo doxaZOsin mesilate, ecadotril; enalapril maleate; risone dibutyrate, ; meSalamine; enalaprilat, enalkiren, endralazine mesilate; epithi meSeclaZone, methylprednisolone Suleptanate; azide, eproSartan, eprosartan mesilate; momiflumate, nabumetone, naproxen; naproxen mesilate; flavodilol maleate; flordipine; floSequinan; Sodium; naproXol; nimaZone; Olsalazine Sodium; foSinopril Sodium; foSinoprilat, guanabenz, guana orgotein, orpanoxin; Oxaprozin, oxyphenbutaZone; benz acetate, guanacline Sulfate; guanadrel Sulfate; paranyline, Sodium; phenbuta guancydine, guanethidine monoSulfate, guanethi Zone Sodium glycerate, pirfenidone, piroXicam, dine Sulfate; guanfacine, guanisoquin Sulfate, gua piroXicam cinnamate, piroXicam olamine, pirprofen; noclor Sulfate, guanoctine, guanoXabenz, , prifelone, prodolic acid; produaZone; Sulfate, guanoxyfen Sulfate; , hydrala proxazole; proxazole citrate, , romazarit; Zine polistirex, , ; Salcolex, Salnacedin; Salsalate, Sanguinarium chlo ; indolaprif, ; indoramin; ride, SeclaZone, Sermetacin; Sudoxicam, Sulindac, , ; leniquinsin; levcromakalim, Suprofen; talmetacin, talniflumate; taloSalate; lisinopril; , losartan; loSulazine, meb tebufelone; tenidap; tenidap Sodium; tenoxicam, utamate; ; medroxalol, medroxalol; teSicam, tesimide, tetrydamine, tiopinac, methalthiazide, , , pivalate; tolmetin, tolmetin Sodium, ; tri methyidopate; metipranolol, ; metoprolol flumidate, Zidometacin, Zomepirac Sodium. fumarate; metoprolol Succinate; metyrosine; minoxi dil; monatepil maleate; ; nebivolol; 0121 Antimalarials: , oformine; ; paZOxide; pel 0.122 acedapSone; ; amduinate; arte anSerin; perindopril erbumine, ; flene, chloroquine; chloroquine; chloroquine phos ; pivopril, , praZosin; primi phate, cycloguanil pamoate, enpiroline phosphate; dolol; prizidilol, quinapril, quinaprilat, quinaZOsin; halofantrine, hydroxychloroquine Sulfate, meflo , , quinuclium bromide, rami quine; menoctone, mirincamycin; primaquine phos pril; rauwolfia Serpentina, , Saprisartan; phate, pyrimethamine; quinine Sulfate; tebuquine. Saralasin acetate, Sodium nitroprusSide, ; tasoSartan; teludipine; temocapril; teraZosin, terla 0123 Microbicides: kiren, , tiamenidine, ticrynafen; Unab 0.124 aztreonam, chlorhexidine gluconate, imi inol, tiodaZoSin; tipentosin; , tri durea, lycetamine, nibroxane, piraZmonam Sodium; maZOsin; trimethaphan camsylate; trimoxamine; ; pyrithione Sodium; Sanguinarium tripamide; , Zankiren, Zofenoprilat arginine. chloride; tigemonam dicholine. 0117 Antihypotensives: 0.125 Antimigraine agents: 0118 ; . 0.126 ; ; ; ; 0119) Antiinfl t t aZatadine, bemeSetron; BIBN4096BS; IIn Ilammatory agentS: BMS-181885; ; dolasetron; donitrip 0120 alclofenac, dipropionate; alge tan; ; ; ; ; Stone acetonide; alpha amylase, , amcina ; IS-159; ; ; fide, amfenac Sodium; amiprilose; anakinra, aniro LY-334370; LY-53857; ; metergotamine; lac, anitraZafen; apaZone; balsalazide disodium; ; ; ORG-GC94, oxetorone; bendaZac, benoxaprofen; benzydamine; bromelains, pipethiadene, ; propisergide, ; broperamole; ; carprofen, cicloprofen; , ; ; tropoxin; cintaZone; cliprofen, propionate, clobeta UK-116044; ; ; . Sone butyrate; clopirac, proplonate; 0.127) Active ingredients for sea sickness and vomit cormethasone acetate; cortodoxone, ; ing: ; ; dexamethasone dipropi onate, diclofenac, diclofenac Sodium; 0128 buclizine; cyclizine lactate; naboctate. diacetate; diflumidone Sodium; diflunisal; diflupred 0129. Cytostatics: nate; diftalone; ; ; endry Sone; enlimomab, enolicam Sodium, epirizole; 0.130 acivicin; aclarubicin; acodazole; acronine; etodolac, etofenamate; felbinac, fenamole; fenbufen, adoZelesin; aldesleukin; altretamine; ambomycin; fenclofenac, fenclorac, fendosal; fenpipalone; fen ametantrone acetate; , amsacrine; tiazac, flazalone; , ; flumi ; anthramycin; asparaginase; asperlin; Zole; acetate; flunixin; flunixin meglu aZacitidine; azetepa, azotomycin; batimastat; ben mine; butyl, acetate; ZOdepa; , bisantrene, bisnafide dimeSi fluguaZone; flurbiprofen; fluretofen, pro late; bizelesin, bleomycin Sulfate, brequinar Sodium; pionate; furaprofen; furobufen, , halobe bropirimine; buSulfan, cactinomycin, ; tasol propionate; acetate, ibufenac, ibu caracemide; carbetimer; carboplatin; carmustine; profen, aluminum; ibuprofen piconol; carubicin; carZelesin, cedefingol, chlorambucil; cir ilonidap; indomethacin; indomethacin Sodium; olemycin, cisplatin, cladribine; crisinatol mesilate; indoprofen; indoxole, intrazole, ; cytarabine, dacarbazine, dacti US 2004/0058896 A1 Mar. 25, 2004

nomycin; daunorubicin; decitabine; deXormaplatin; 0.135 Antiproliferative active ingredients: de Zaguanine; de Zaguanine mesilate; diaziquone; 0.136 piritreximisethionate. , doxorubicin, doxonubicin; , droloxifene citrate; dromoStanolone propionate; dua 0.137 Antiprotozoal active ingredients: Zomycin, edatrexate, eflomithine; elsamitrucin; 0.138 amodiaquine; azanidazole; bamnidazole; enloplatin; enpromate, epipropidine, epirubicin; carnidazole; chlortetracycline bisulfate, chlortetra erbulozole; eSorubicin; , estramusUne cycline; flubendazole; flunidazole; halofuginone phosphate Sodium; etanidazole; ethiodized oil I 131; hydrobromide, imidocarb; ipronidazole; metronida etoposide; etoposide phosphate, etoprine, ; Zole; misonidazole; moxnidazole, nitarSone; partri fazarabine; fenretinide; floxuridine; fludarabine cin; puromycin; puromycin; ronidazole, Sulnidazole; phosphate; fluorouracil; flurocitabine; fosquidone; tinidazole. fostriecin Sodium; gemcitabine; gemcitabine; 0.139 Active ingredients for treating pruritus: Au 198; hydroxyurea; idarubicin; ifosfamide, ilmo fosine; interferon alfa-2a, interferon alfa-2b; inter 0140 cyproheptadine; ; methdilazine; feron alfa-n1; interferon alfa-n3, interferon beta-I a. trimeprazine tartrate. interferon gamma-Ib, Iproplatin, irinotecan; lan 0141 Psoriasis active ingredients: reotide acetate; ; leuprolide acetate; liaro Zole, lometrexol Sodium, lomustine; loSOXantrone; 0.142 acitretin; anthralin; azaribine; calcipotriene; masoprocol; maytansine; mechlorethamine; mege cycloheximide, enaZadrem phosphate, etretinate; Strol acetate; acetate; melphalan; liarozole fumarate; lonapalene; tepoxalin. menogaril; mercaptopurine, methotrexate, methotr 0143 Neuroleptics: exate Sodium; metoprine, meturedepa; mitindomide, 0144) maleate; hydrobro mitocarcin, mitocromin, mitogillin, mitomalcin, mide; alpertine, ; batelapline maleate; ben mitomycin, mitosper, mitotane, mitoxantrone; peridol; benzindopyrline; brofbxine; ; mycophenolic acid; ; nogalamycin; bromperidol decanoate, , ; ormaplatin, OXisuran, , pegaspargase, butaperazine maleate, carphenazine inaleate; car peliomycin; pentamustine, peplomycin Sulfate; per Votroline, chlorpromazine, chlorpromazine, chlor fosfamide, pipobroman; pipOSulfan, piroXantrone; prothixene, cinperene, cintriamide; comacran phos ; ; porfimer Sodium; porfiro phate; ; , clopipazan mycin; ; , puromycin; mesilate; cloroperone; clothlapine; clothixamide puromycin; pyrazofurin, riboprine, ; maleate; , cyclophenazine, ; eta Safmgol, Safingol, Semustine, SimtraZene, Sparfosate Zolate; fenimide; ; , fluphena Sodium, SparSomycin; Spirogermanium; Spiromus Zine decanoate, enanthate; fluphena tine, Spiroplatin; Streptonigrin, Streptozocin, Stron Zine; fluspiperone; , flutroline; tium chloride Sr 89; Sulofenur; talisomycin; taxane; ; halopemide; ; haloperidol taxold; tecogalan Sodium, tegafur, teloxantrone; decanoate, , imidoline; ; maza temoporfin, teniposide; teroxirone; ; pertine Succinate; , meSoridazine besy thiamiprine; thioguanine; thiotepa, tiazofurin; tira late; , milenperone; millipertine; molin paZamine; topotecan; toremifene citrate; trestolone done; , neflumozide, ; acetate, triciribine phosphate, trimetrexate, trimetr , OXiperomide; ; pentiapine exate glucuronate, triptorelin; tubulozole, uracil maleate; ; , ; pipam ; uredepa, Vapreotide; verteporfin, vinblas perone, , painlitate; tine Sulfate; Vincristine Sulfate; Vindesline, Vindesline ; prochlorperazine edisylate; prochlor Sulfate; Vinepidine Sulfate; Vinglycinate Sulfate; Vin perazine maleate; , ; remox leurosine Sulfate; Vinorelbine tartrate; Vinrosidine ipride, ; Seperidol, Sertindole, ; ; ; thioridazine; thiothixene; Sulfate; Vinzolidine Sulfate; Vorozole; Zeniplatin; thiothixene, tioperidone, ; ; Zinostatin; Zorubicin. , , triflu promazine; 0131 Active ingredient for combination therapy with . cytostatics: 0145 Antirheumatics: 0132) and desipramine. 0146 auranofin; aurothioglucose; bindarit; loben 0.133 Antiparkinson agents: Zarit Sodium; phenylbutaZone, piraZolac, prinomide tromethamine; Seprilose. 0134) benztropine mesilate; biperiden; biperiden; 0147 Antischistosomal agents: biperiden lactate; carmantadine, , dopaman tine, ethopropazine, lazabemide; levodopa, lometra- 0.148 becanthone; hycanthone; lucanthone; nirida line, ; naxagolide, pareptide Sulfate; pro- Zole; ; pararosaniline pamoate, terOX cyclidine, quinetorane; , ; alene. ; trihexyphenidyl, antiperistaltic, difenox imide; difenoxin; diphenoxylate; fluperamide, lida 0149 Active ingredients for treating seborrhea: midine; ; malethamer, nulfenoXole, par- 0150 ; piroctone; piroctone olamine; egoric. resorcinol monoacetate. US 2004/0058896 A1 Mar. 25, 2004 10

0151. Antispasmolytics: 0164. Other antiulcer agents 0.165 ; AD-1308; benex 0152 stilonium iodide; . ate, benzotript, beperidium iodide, ; 0153 Antithrombotics: BTM-1086; cadexomer iodine, cetraxate; CF-19415; CHINOIN-127; darenzepine; deboxamet; detralfate; 0154) argatroban; ; bivalirudin; dalteparin DH-6615; doSmalfate, ecabapide, ecabet; eSapra Sodium; domitroban; daltroban; danaparoid Sodium; Zole, espatropate, gefamate; , KW-5805; daZOXiben; E-3040; efegatran Sulfate; enoxaparin lactalfate; loZilurea; MAR-99; MCI-727; Sodium; ifetroban; ifetroban Sodium; KW-3635; MDL-201034; mezolidon; molfamate; nolinium bro LCB-2853; linotroban; mipitroban; NM-702; pico mide; nuVenzepine; octreotide, P-1100; pifamine; tamide, ; ridogrel, S-1452, Samixogrel; , plaunotol; polaprezinc, rebamipide; ; Sulotroban; ; Unzaparin RGH-2961; rispenzepine; rotraxate; ; Sodium, trifenagrel. SiltenZepine; Sofalcone, Sucralfate, SucroSofate; Sulglicotide; ; ; teprenone; 0155 Antitussives: tiopropamine; tolimidone; triletide, tritioZine; troX ipide; UH-AH-37; Zolenzepine; Zolimidine. 0156 ; ; bibenzonium bro mide, , citrate; butetamate; 0166 Agents for treating urolithiasis: ciobutinol, chlofedanol, codeine, codeine polistirex, 0.167 benzoic acid; cysteamine; cysteamine; trici codoxime; ; dextromethorphan trateS. polistirex, dihydrocodeine; , dro- 0168 Virustatic agents: propizine; drotebanol, ; ethyl ; ; gualapate, ; hydrocodone 01.69 abacavir; acemannan; aciclovir; adefovir; alo Vudine, alvircept Sudotox; , , polistireX, iQuindamine; ; levdropropizine; aranotin; arildone; atevirdine; avridine; BW-935 napSylate; medazomide, mepro U83; calanolide B; cidofovir; cipamfylline; cytara tiXol; ; , ; noScap bine; DAPD; ; desciclovir, didanosine; ine, pemerid nitrate; , , disoxaril; DPC-083; edoxudine; , emivir picoperine, ; , promolate; ine, enviradene, enviroxime; famciclovir, famotine; Saredutant, Sodium dibunate, Suxemerid Sulfate; the flacitabine; fialuridine, fosarilate; foScarnet Sodium; bacon, , Vadocaine, . fosfonet sodium; ganciclovir; GW-420867X; idoxu ridine, kethoxal; L-697661; lamivudine; lobucavir; O157 Antiulcer agents: memotine; methisazone; ; NSC-678323; 0158 H2 antagonists penciclovir, pirodavir, ribavirin, , S-1153; Saquinavir, Somantadine, Sorivudine, Stato 0159) BL-6271; BL-6341A; BMY-25368; lon; Stavudine, talviraline; thioctic acid; tillorone; BRL-28390; ; dalcotidine; donetidine; trifluridine; troVirdine, U-93923; valaciclovir; ; etintidine; ; ICI-162846; ico- Vidarabine, Vidarabine, Vidarabine, ViroXime; Zalcit tidine; IGN-2098; isotiquimide; ; lamti- abine, Zidovudine, ZinviroXime. dine; ; , mifentidine, niperoti dine, , OSutidine, , pibubdine, 0170 Active ingredients for treating benign pifatidine, ramixotidine, , ranitidine bis hyperplasia: muth citrate, ranitidine nitrate, roXatidine, Sufoti- 0171 alfuzosin; CEP-701; doxazosin; ; dine; TAS, tiotidine; venritidine; WHR-2348; FK-143; GI-231818; GYKI-16084; levormelox YM-14471; Zaltidine; . ifene; pirfenidone; RS-97078; tamsulosin; sito gluSid. 0160 Proton pump inhibitors 0172 Active ingredients for treating : 0161 disuprazole; esomeprazole; FPL-65372-XX; alendronic acid; butedronic acid; clodronic acid; H-335/25; H-405/02; HN-11203; IY-81149; lanso EB-1053; etidronic acid; ibandronic acid; incadronic prazole, leminoprazole; lucartamide, N-2220, acid; medronic acid; minodronic acid; neridronic acid; NC-1300; nepaprazole, , pantoprazole; olpadronic acid, oxidronic acid; pamidronic acid; piri pantoprazole Sodium, picartamide, picoprazole; dronic acid; ranelic acid; risedronic acid; tiludronic pumaprazole; rabeprazole; saviprazole; SCH-28080; acid; YM-529; Zoledronic acid. SKF-95-601, SKF-96067; SKF-97574; T-330; T-776; tenatoprazole; ufiprazole; YH-1885; 0173 Carbonic anhydrase inhibitors: YM-1902O. 0.174 ; AL4414A, diclofenamide; dorZolamide, methazolamide, SeZolamide, Sulocar 0162 Prostaglandins bilate. 0163 arbaprostil; butaprost; deprostil; dimethyidi- 0175 Antiarrhythmics: noprostone; dimoxaprost, enisoprost, enprostil, 0176 abanoquil; ACC-9164; acecainide; actiso mexiprostil; misoprostol; nocloprost, ornoprostil; mide, , , alinidine, ; Oxoprostol; remiprostol, rioprostil; rosaprostol; alprafenone; amafolone; ambasilide; ameltolide, SC-30249; spiriprostli; TEI-1226; tiprostanide; tri- amiodarone, , aprindine, artilide, moprostil, asocainol; AWD-G-256; ; benderizine; ben US 2004/0058896 A1 Mar. 25, 2004 11

rixate, benzodioxine, berlafenone; bertosamil, bidi dibuprol; epomediol; exiproben, febuprol, fenci Somide; bisaramil, BRL-32042; bucainide; bucro butirol; femipentol; hexacy prone; ; marone; ; buduineran; butobendine, menbutone, moduizone, piprozolin; proZapine, Sin butoprozine, capobenic acid; carbizocaine; calide; tenylidone; terbuprol; tocamphyl, trepibu carcainium chloride; cariporide; carocainide; tOne. cercainide, cibenzoline, cifenline, ciprafamide, CL-284027; clamikalant; clofilium phosphate; 0181 Cholinergic agents: CV-6402; CVT-510; cyclovirobuxine-D, D-230; 0182 acedidine; bethanechol chloride; ; detaJmium bitartrate; disobutamide, deXSotalol; demecarium bromide; dexpanthenol; echothiophate dioxadillol, ; disobutamide, disopyra iodide, isoflurophate, methacholine chloride, neo mide; dolfetilid; drobuline, ; droXicain Stigmine bromide; neoStigmine methylsulfate, phy ide; E047/1, E-0747; E4031; edifolone; emilium SoStigmine, phySOSugmine Salicylate; phySOSugmine tosilate, ; , eproXindine, erocain Sulfate; pilocarpine, pilocarpine, pilocarpine nitrate; ide, ; fepromide, ; fluZoperide; pyridostigmine bromide. gallanilide, glemanserin; guaifecainol, GYKI-23107; GYKI-38233; heptacaine; hydroxyfenone; ibutiide; 0183 Cholinergic agonists: ; ipazilide, itrocainide, ketocainol; 0.184 xanomeline; xanomeline tartrate. L-702958; L-706000; levosemotiadil; ; lorcainide; meobentine, ; milacainide; 0185. inhibitors: modecainide; ; moxaprindine, murocain 0186 ; DMPS; ; ide, nibentan; nicainoprol; nipekalant, nofecalnide; chloride, chloride, prali oxiramide, palatrigine; penticainide; pentisomide, doXime iodide, pralidoxime mesilate. , pirmenol; pirolazamide, prajmalium bitartrate, pranolium chloride; prifuroline, procaina 0187 Coccidiostats: mide, ; pyrinoline; quinacainol, quindo 0188 aklomide; amidapSone; amprolium; nium bromide, , recainam, riloZarone; riso arprinocid; bitipaZone; buduinolate, ciadox, claZuril; tilide, ronipamil; ropitoin, Sematilide, ; dopidol, decoquinate, diciaZuril, dinitolamide, Solpecainol, , Stirocainide; Stobadine, dinsed; halofuginone; letraZuril, narasin; nequinate; SR47063; Sulamserod; Suricainide; tedisamil; nicarbazine; nifurSemizone, ponaZuril; produinolate; terikalant; tiracizine, ; toSifen, transcainide; robenidine, Semduramicin; SulaZuril; Sulfanitran; tia trecetilide; Zocainone. Zuril; toSulur. 0177 Cardiotonics: 0189 : 0.178 acadesine; acetylidigitoxin; acetyldigoxin; 0.190 acetazolamide; acetothiazide, alipamide; acrihellin; actodigin; ; ; amse , amanozine; ; ambuSide; lamine; ; arpromidine; AWD-122-239; ; aminometradine, amisometradine, ampy bemoradan; ; butopamine; carbaZeran; rimine; apaxifylline; azolimine; , bemetiz cariporide; carperitide; carsatirin; CGS-13928C; cilo ide; bemitradine; bendroflumethiazide, ; bradine; CK-2130; CK-2289; colforsin; CV-6402; benzolamide; benzthiazide; benzylhydrochlorothiaz , deslanoside; , digitalis, ide, beSulpamide, beSunide, brocrinat; ; ; ; , dobutamine, docar , ; carmetizide, chlorazanil; pamine; domipizone, ; doridosine, chlorothiazide, chlorthalidone, cicletanine, cla aminol; DPI-201-106; draflazine; eniporide; enoxi Zolimine; clopamide; ; CVT-124; dicir mone; ER-21355; evodiamine; ; FK-664; enone; disulfamide; , ethacrynate fosfructose; FR-113453; FR-46171; gapromidine; Sodium, ethacrynic acid; etofylline, ; fen gitaloxin; gitoformate; JP-1-468; GP-1-531; quizone; FK-352; FR-113453; ; hydro GP-668; ; , ; ima chlorothiazide, hydroflumethiazide, indacrinone; Zodan; indolidan; isamoltan; isomazole; levacecar indapamide; isosorbide; KW-3902; lemidosul, man nine; levdobutamine; ; limaprost, lin nitol; , ; methalthiazide, meth sidomine; lixazinone; MCI-154, medorinone; aZolamide; methydothiazide, ; metola meproscillarin; meribendan; metildigoxin; mildr Zone; muzolimine; niravoline; OPC-31260; onate; ; mioflazine; mixidine, MS-857; oXprenoate; ; paraflutizide, penflutizide, nanterinone; neraminol; NKH-477; olprinone; OPC ; polythiazide, canrenoate; propazolamide; 18750; otenZepad; Oxfenicine, peirinone; pengi prorenoate; prorenone, pytamine, quincarbate; toxin; pentrinitrol; peruvosid; ; piroxi ; RPH-2823; S-8666; sitalidone; mone, pirSidomine; prinoXodan; prisotinol, Spironolactone, Spirorenone, SpiroXaSone; SR48692; propionylcamitine, proscillaridin; quaZinone; quaZo Sulciamide, Sullicrinat, Sulocarbilate, Sulosemide, dine, quindonium bromide, ramnodigin; revizinone; Sumetizide, teclothiazide, tiamizide, ; Saterinone, ; Simendan; Sulmazole; thev torSemide, , trichlormethiazide, triflocin, etosid; toborinone; ubidecarenone, ; tripamide; TRK-820; ularitide; ; Xipamide. VPA-985. 0191) Ectoparasiticides: 0179 Choleretic agents: 0.192 carbaril; clidafidine, ; epri 0180 alibendol; azintamide; boldine, cicloxilic nomectin; fenclofoS, fenvaierate; ivermectin; lin acid, cinametic acid; clanobutin, dehydrocholic acid; dane; moxidectin; nifluridide, , temefoS. US 2004/0058896 A1 Mar. 25, 2004 12

0193 Emetics: rometholone; flupameSone; acetate; flu prednidene, ; fluprednisolone Valer 0194 . ate, flurandrenolide; fluticaSone; fluticasone 0195 inhibitors: propionate; ; ; GW-215864X ; GW-250945; halcinonide; halocor 0196) acetohydroxamic acid; alrestatin Sodium; tolone; ; halopredone acetate, hydro aprotinin; benazepril; benazeprilat, benurestat; bro cortamate; ; ; mocriptine, bromocriptine mesilate; cilastatin , ; Sodium; flurofamide, , lergotrile mesilate; , hydrocortisone enbutate; levcycloSerine; libenzapril, pentopril, pepstatin; per hydrocortisone Sodium phosphate, hydrocortisone indopril, polignate Sodium, Sodium amylosulfate; Sodium Succinate, , icometa Sorbinil; Spirapril; Spiraprilat, ; teprotide; Sone enbutate, isoflupredone; , itroci tolfamide, Zofenopril calcium. nonide; locicortolone, locicortolone dicibate; 0197) : loteprednol etabonate; ; ; ; ; methylprednisolone; 0198 ; ; diethylstil methylprednisolone acetate, methylprednisoloXime bestrol; diphosphate, ; Sodium phosphate, methylprednisolone Sodium Suc ; , ; estradiol cinate; furoate, naflocort; ; enanthate, ; ; nivaZol; acetate; prednazate; predna hydrobromide, , , estro Zoline; ; ; ; gens, conjugated; estrogens, esterified; ; ; prednisolone fameSylate; pred ; ethinyl estradiol, ; ; nisolone hemisuccinate; prednisolone Sodium phos nylestriol, phate, prednisolone Sodium Succinate; prednisolone 0199 Fibrinolytics: tebutate; ; , ; 0200 aceXamic acid; amediplase; anistreplase; prednival; procinonide, , rimeXolone, rof aprotinin, bisobrin lactate, brinase, brinolase, camo leponide; TBI-PAB; propionate; timobe Stat; fibrinolysin; inicarone, iquindamine, nattoki Sone; tipredane; tiXocortol; ; tral nase, pamiteplase, picotamide, Staplabin; Streptoki onide, ; ; triamcinolone acetonide Sodium, triamcinolone nase; ; tizabrin; tranexamic acid; benetonide, ; triamcinolone 0201 Free-radical scavenger: furetonide; triamcinolone hexacetonide; triclonide; 0202 pegorgotein. . 0203 Motility-increasing active ingredients: 0207 Hemostatics: 0204 (Propulsid); metoclopramide 0208 aminocaproic acid; oxamarin; Sulmarin; (Reglan), hyoscyamine (Levsin). thrombin; traneXamic acid. 0209 : diethylstilbestrol; progesterone; 0205) Glucocorticosteroids: 17-hydroxy progesterone; ; norg 0206 ; alclometasone; estrel; norethynodrel; estradiol; (Megace); acetonide, amcinafal, , , ame norethindrone; ; ethyndiol, ethinyl estra bucort, , beclomethasone dipropi diol, mestranol; estrone, equilin; 17-alpha-dihy onate, bendazacort, ; betamethasone droequilin; ; 17 alpha dihydroeguilenin, acetate; ; betamethasone 17-alpha-estradiol; 17-beta-estradiol; leuprolide diproplonate, betamethasone Sodium phosphate, (lupron); glucagon; testolactone; clomiphene; han ; budesonide; ; memopausal , human chorionic gonadot butxocort propionate; CGP-13774; ; ropin; urofollitropin; bromocriptine; gonadorelin; ciclometasone, ciprocinonide; clobetasol, clobetasol luteinizing releasing hormone and analogs, 17-propionate, ; acetate; gonadotropins, ; testosterone, dehydroepi , ; cloticasone; cloti ; , dihydroestosterone; casOne propionate, CMJ, ; corticotro relaxin, oxytocin, Vasopressin, folliculostatin, follicle pin; corticotropin; corticotropin Zinc hydroxide; cor regulatory ; gonadoctrinins; oocyte maturation tisone acetate; cortisu Zol; ; deflazacort; inhibitor; insulin growth factor; follicle Stimulating , deprodone propionate, hormone; luteinizing hormone, tamoxifen, corticorelin acetonide; desonide; desoximetasone; desoxycor Ovine triftutate; coSyntropin; , pituitary, pos tone; dexamethasone; ; terior, Seractide acetate, Somalapor, Somatrem; Somat dexamethasone Sodium phosphate; ; ropin; Somenopor, Somidobove. ; diflorasone; ; diflucor 0210 HMG-CoA reductase inhibitors: tolone pivalate; , ; domopred 0211 (Mevacor); (Zocor); nate, ; drocinonide; FSDCICM; fluaza pravastatin (Pravachol); fluvasatin (Lescol). cort, acetonide; flucloronide; fludrocortisone; fluidroxycortide; ; flu 0212 Immunomodulators: metaSone pivalate; flumoxonide; flunisolide; fluoci 0213 dimepranol acedoben; imiquimod; interferon nolone acetonide; ; fluocortin; fluocortin beta-lb., , mycophenolate mofetil, preza butyl, ; fluocortolone caproate; fluo tide acetate. US 2004/0058896 A1 Mar. 25, 2004 13

0214) Immunoregulators: 0232) Mydriatics: 0215 azarole; mesilate; frentizole; 0233 . oxamisole, ristianol phosphate; thymopentin; tilomi 0234 Neuroprotective agents: Sole. 0235 maleate. 0216) Immunostimulants: 0236 NMDA antagonists: 0217) loxoribine, teceleukin. 0237 ACPC; ; BMY-14802; CGP-37849; 0218) ImmunosuppreSSants: CP-101606; dizocilpine; EAA-090; ; fel bamate; FPL-12495; ; harkoseride; 0219 azathioprine; azathioprine Sodium; cycloSpo HU-211; ipenoxazone; L-695902; ; rine; daltroban, gusperimus trihydrochloride; Siroli ; ligustizine; midafotel; milnacipran; mus, . nebostinel; , , Seratrodast; Sper 0220 Active ingredients for treating impotence: midine; ; UK-240255; ZD-9379. 0221) abanoquil; alproStadil; amlodipine; 0238) Nonhormonal derivatives: BMS-193884; deleguamine, doxazosin, E-4010; 0239 . trinitrate; IC-351; melanotan II; ; nitraguaZone; , phenoxybenzamine, pra 0240. Oxytocics: Zosin, quinelorane, , UK-114542; urapidil; 0241 carboprost; carboprost methyl; carboprost ; VIP; yohimbin; tromethamine, dinoprost, dinoprost tromethamine; dinoprostone; ergonovine maleate; meteneprost; 0222 LHRH antagonists: methylergonovine maleate; oxytocin, Sparteine Sul 0223 deslorelin; ; histrelin; lutrelin fate. acetate, nafarelin acetate. 0242 Plasminogen activators: 0224 Hepatoprotectant: 0243) alteplase; urokinase. 0225) malotilate. 0244 PAF antagonists: 0226 Luteolytics: 0245) lexipafant. 0227 fenprostalene. 0246 Aggregation inhibitors: 0247 acadesine; beraprost; beraprost sodium; 0228 Cerebrotonics: ciprostene calcium; itaZigrel, lifarizine, OXagrelate. 0229 aloracetam; alvameline; ; apaxifyl 0248 Progestins: line, aptiganel; azetirelin; brovincamine, cebarac etam; cevimeline; CI-844, CI-933; demiracetam; 0249 ; acetate; dimoxamine, ; dupracetam, edaravone, acetate, acetate, cinges ; fasoracetam; FK-960, gavestinel; tol, acetate; acetate; ; muracetam; IOS-11212; JTP4819; KST. ; ; ; 5410; leteprinim; ligustizine; ; MCI-225; , ethynodiol diacetate, ; milameline; MKC-231; NDD-094; nebracetam; flurogestone acetate, ; , gesto nicoracetam; nizofenone; ONO-1603; OP-2507; norone caproate, ; ; OPC-14117, , pikamilone, ; hydroxyprogesterone caproate; levonorgestrel; piraXelate, pirglutargine; ; , ; , medroxyprogesterone quiloStigmine, ribaminol, , rolzirac acetate; methynodiol diacetate; norethindrone; nore etam; sabcomeline; sapropterin; SIB-1553A; thindrone acetate, norethynodrel; norgestimate; Sibopirdine; sipatrigine; SM-10888; SNK-882; , ; phen SR-46559-A; stacofylline; T-588; T-82; TAK-147; proplonate; progesterone, acetate; talsaclidine; taltirelin; tamitinol, tenilsetam; Vincon ; . ate; ; ; Xanomeline; YM-796; 0250) Prostate growth inhibitors: YM-900; Z-321; Zifrosilone. 0251 . 0230. Mucolytics: 0252) Prothyrotropin: 0231 ; adamexine; ; ben 0253) protirelin. cisteine, bromheXine, brovanexine, carbocysteine; cartasteine, cistinexine, dacisteine, danosteine, dem 0254 Psychotropic agents: brexine, ; , erythromycin Sal 0255 minaprine. nacedin, erythromycin Stinopate, guaimeSal; IDB 1031; isalsteine; , , ; 0256 Calcium regulators: mideSteine, mogulsteine, meltenexine, neSOsteine; 0257 alfacalcidol; calcifediol; calcipotriol; calcito omonasteine, OXabrexine, prenisteine, Salmisteine; nin; calcitriol, dihydrotachysterol, doxercalciferol; , tasuldine, taurosteine; telmesteine, tiopro falecalcitriol, leXacalcitol; maxacalcitol, Secalcif erol, Seocalcitol; tacalcitol; US 2004/0058896 A1 Mar. 25, 2004 14

0258 Relaxants: , hydrochlo ride; , , , Xamot 0259 adiphenine; alcuronium chloride; aminophyl erol, Xamoterol fumarate. line, azumolene Sodium; ; ; ; chlorphenesin ; chlorZOX 0276 Suppressants: aZone, cinflumide, , clodanolene; cyclobenzapine, dantrolene, dantrolene Sodium; 0277 amflutizole; coxchicine, taZofelone. fenalamide, fenyripol, fetoxylate; , fle 0278 Active ingredients for treating symptomatic tazepam, flumetramide;-, hexafluorenium multiple Sclerosis: bromide, isomylamine; ; mebeverine; 0279 fampridine. meSuprine, metaxalone, methocarbamol, methixene; nafomine malate, neleZaprine maleate, papaverine; 0280 Synergistic agents: pipoxolan, quinctolate; ; ritodrine; rolodine, theophylline Sodium glycinate; thiphenamil; xilo 0281 . bam. 0282) hormones: 0260 Scabicides: 0283) Sodium; liothyronine Sodium; liotrix. 0261 , crotamiton. 0284) Thyroid Inhibitors: 0262 Sclerosing agents: 0285) methimazole, propyithiouracil. 0263 clobenoside; ethanolamine oleate; morrhuate 0286 Thyromimetics: Sodium, olamine; tribenoside. thyromedan. 0264 : 0287) 0288 Tranquilizers: 0265 . 0289 ; ; ; 0266 Hypnotics/sedatives: ; , dipotassium; clo 0267 ; alonimid; ; amobar razepate monopotassium; , deXmedeto bital Sodium; , , ; midine, , , hydroxyphenamate; butabarbital sodium; but albital; capuride; carboclo hydroxy Zine, hydroxy Zine pamoate, ; ral, betaine, ; chlordiazep , lorZafone, ; loxapine Succinate; oxide; cloperidone; clorethate, , dex , , ; , pen clamol, , , ; tabamate, piremperone, , roliprarn, , , , , , taciamine; , , , ; , , , Vainoctamide. ; ; ; 0290 Agent for treating cerebral ischemia: midaflur, ; ; pentobarbital Sodium; , , , 0291 . , roletamide, ; Secobarbital 0292 Agent for treating Paget’s disease: Sodium; ; , ; trepi pam maleate; , tricetamide, 0293) tiludronate disodium. Sodium, trimetozine; , ; , tartrate. 0294) Uricosuric agents: 0295) benzbromarone; irtemazole; ; 0268 Selective adenosine A1 antagonists: Sulfinpyrazone. 0269 apaxiyline 0296 Vasoconstrictors: 0270 antagonists: 0297 adrenalone; amidefrine mesilate; angiotensin amide; cafaminol; cilutazolin; clonazoline; cor 0271 tartrate; , ; badrine, domaZoline, epinephrine, epinephryl , tropanserin borate; fenoxazoline; indanazoline, ; 0272) Serotonin Inhibitors: methySergide, metizoline, metrafazoline; naphazo line, riemazoline, Oxedrine; ; phe 0273 ; ; fonazine mesilate; namazoline; , phenylpropanolamine tosylate. polistirex, tefazoline, tetry Zoline; tinazoline; trama 0274 : Zoline, . 0275 ; sulfate; ampy 0298 Vasodilators: Zine Sulfate; arbutamine, azabon, , ceru 0299 alprostadil; azaclorzine; bamethan sulfate; letide; ceruletide diethylamine, cisapride; ; buterizine, cetiedil citrate, chromonar, fumarate; ; dextroamphetamine clonitrate, diltiazem; ; droprenilamine; Sulfate; difluanine; dimefline; ; erythrityl tetranitrate; ; ; foste etryptamine acetate; ethamivan, ; fluba dil; heXobendine, inositol niacinate, iproxamine; nilate; ; histamine phosphate; indriline; isosorbide dinitrate, isosorbide mononitrate; isoxSu US 2004/0058896 A1 Mar. 25, 2004 15

prine; , mefenidil, mefenidil fumarate; patent documents which relate to compounds which inhibit mibefradil dihydrochloride; mioflazine; mixidine; gastric acid Secretion and have a , imidazol,2-a nafronyl oxalate, , , nic pyridine, 7,8,9,10-tetrahydroimidazo[1,2-h1,7naphthyri orandil; ; , ; dine or 7H-8,9-dihydropyrano 2,3-climidazo[1,2-alpyridine , Oxfenicine; OXprenolol, pentaerythritol basic Structure. tetranitrate; , pentrinitrol; maleate; pindolol, pirSidomine; ; pro 0306 Examples of reversible proton pump inhibitors or patyl nitrate, Suloctidil; ; tipropidil; tolaZo APAS which should be mentioned as preferred are, interalia: line, Xanthinol niacinate. 0307 AU-461 2-1-(2-methyl-4-methoxyphenyl)-6- (2.2.2-trifluoroethoxy)-2,3-dihydro-1H-pyrrolo3.2-c 0300 Active ingredients for wound healing: quinolina-ylamino-1-, 0301) erSofermin. 0308) DBM-819 3-1-(4-methoxy-2-methylphenyl)- 0302 Xanthine oxidase inhibitors: 6-methyl-2,3-dihydro-1H-pyrrolo-3,2-cquinolin-4- ylamino1-propanol, 0303) allopurinol, oxypurinol 0309 KR-60436 (2-1-(4-methoxy-2-methylphenyl)- 0304. In a preferred embodiment of the invention, the 6-(trifluoromethoxy)-2,3-dihydro-1H-pyrrolo3.2-c active ingredient is a PDE (phosphodiesterase) inhibitor, quinolin-4-ylaminoethanol, particularly preferably PDE 4 inhibitor, especially N-(3.5- dichloropyrid-4-yl)-3-cyclopropylmethoxy-4-difluo 0310) R-105266; YJA-20379-8 (+)-1-8-ethoxy-4-(1 romethoxybenzamide (INN: roflumilast) its N-oxide or a (R)-phenylethyl)amino-1,7-naphthyridin-3-yl)-1-bu pharmacologically suitable salt of roflumilast or of its N-ox tanone), ide. The preparation of N-(3,5-dichloropyrid-4-yl)-3-cyclo 0311 8-(2-methoxycarbonylamino-6-methylbenzy propylmethoxy-4-difluoromethoxybenzamide, its pharma lamino)-2,3-dimethylimidazol,2-apyridine, cologically Suitable Salts and its N-oxide, and the use of these compounds as phosphodiesterase (PDE)4 inhibitors is 0312 3-hydroxymethyl-8-(2-methoxycarbonylamino described in the international application WO95/01338. In a 6-methylbenzylamino)-2-methylimidazol,2-a-pyri particularly preferred embodiment of the invention, the dine, active ingredient is a phosphodiesterase (PDE) 3/4 inhibitor, in particular (-)-cis-9-ethoxy-8-methoxy-6-(4-diisopropy 0313 3-hydroxymethyl-8-(2-methoxycarbonylamino laminocarbonylphenyl)-2-methyl-1,2,3,4,4a, 10b-hexahy 6-methylbenzyloxy)-2-methylimidazo1,2-a-pyridine, drobenzoc1,6naphthyridine (INN: pumafentrine). The 0314 8-(2-methoxycarbonylamino-6-methylbenzy preparation of (-)-cis-9-ethoxy-8-methoxy-6-(4-disopropy loxy)-2,3-dimethylimidazol,2-apyridine, laminocarbonylphenyl)-2-methyl-1,2,3,4,4a,10b-hexahy drobenzoc1,6naphthyridine and its pharmacologically 0315 8-(2-tert-butoxycarbonylamino-6-methylbenzy Suitable Salts, and the use of this compound as phosphodi lamino)-2,3-dimethylimidazol,2-apyridine, esterase (PDE) 3/4 inhibitor is described in the International 0316 8-(2-tert-butoxycarbonylamino-6-methylbenzy application WO98/21208. loxy)-2,3-dimethylimidazol,2-apyridine, 0305 The matrix of the invention is outstandingly suit able as dosage form for active ingredients from the class of 0317 8-(2-ethoxycarbonylamino-6-methylbenzy substances known as reversible H', K"-ATPase inhibitors, lamino)-2,3-dimethylimidazol,2-apyridine, which are also referred to as reversible proton pump inhibi 0318 8-(2-isobutoxycarbonylamino-6-methylbenzy tors or APAS (acid pump antagonists). Reversible proton lamino)-2,3-dimethylimidazol,2-apyridine, pump inhibitors or APAS are disclosed, for example, in the patent document DE-A 3917232, EP-A-0399267, EP-A- 0319 8-(2-isopropoxycarbonylamino-6-methylbenzy 0387821, JP-A-3031280, JP-A-2270873, EP-A-0308917, lamino)-2,3-dimethylimidazol,2-apyridine, EP-A-0268989, EP-A-0228006, EP-A-0204285, EP-A- 0320 8-(2-tert-butoxyarbonylamino-6-methylbenzy 0.165545, EP-A-0125756, EP-A-0120589, EP-A-0509974, lamino)-3-hydroxymethyl-2-methylimidazol,2-a-py DE-A3622036, EP-A-0537532, EP-A-0535529, JP-A- ridine, 3284.686, JP-A-3284622, U.S. Pat. No. 4,833,149, EP-A- 0261912, WO-A-9114677, WO-A-9315055, WO-A- 0321 8-(2-tert-butoxycarbonylamino-6-methylbenzy 9315071, WO-A-9315056, WO-A-9312090, WO-A- loxy)-3-hydroxymethyl-2-methylimidazol,2-a-pyri 9212969, WO-A-9118887, EP-A-0393926, EP-A-0307078, dine, U.S. Pat. No. 5,041,442, EP-A-0266890, WO-A-94.14795, EP-A-0264883, EP-A-0033094, EP-A-025.9174, EP-A- 0322 8(2-(2-methoxyethoxy)carbonylaminol-6-me 0330485, WO-A-8900570, EP-A-03681.58, WO-A- thylbenzyloxy)-2-methylimidazo1,2-alpyridine-3- 9117164, WO-A-9206979, WO-A-9312090, WO-A- , 9308.190, U.S. Pat. No. 5,665,730, DE-A3011490, U.S. Pat. 0323 8(2-(2-methoxyethoxy)carbonylaminol-6-me No. 4,464,372, EP-A-0068378, WO-A-9424130, U.S. Pat. thylbenzylamino)-2-methylimidazol,2-a-pyridine-3- No. 5,719,161, U.S. Pat. No. 6,124,313, WO-A-9527714, methanol, WO-A-9617830, WO-A-9837080, WO-A-9955705, WO A-9955706, WO-A-0010999, WO-A-0011000, especially in 0324 8-(2-(2-methoxyethoxy)carbonylaminol-6-me the documents WOA-9842707, WO-A-98.54188, WO-A- thylbenzylamino2,3-dimethylimidazol,2-a-pyri 0017200, WO-A-0026217 and WO-A-0063211, and in other dine,

US 2004/0058896 A1 Mar. 25, 2004

Salts with bases which may be mentioned are Sodium, 0403. The triglyceride is glycerol with its three hydroxyl , magnesium or calcium Salts. If the acid-labile groups esterified by carboxylic acids. The carboxylic acids proton pump inhibitors are isolated in crystalline form, they are preferably monobasic carboxylic adds with 8 to 22 may contain variable amounts of Solvent The term acid , preferably naturally occurring carboxylic labile proton pump inhibitor therefore also represents acids. It is possible in this case for the carboxylic acids to be according to the invention all Solvates, in particular all different or, preferably, identical. Examples which may be hydrates, of the acidlabile proton pump inhibitors and their mentioned are tristearate, tripalmitate and, particularly pref Salts. Such a hydrate of the Salt of an acid-labile proton pump erably, trimyristate (these triglycerides are commercially inhibitor with a base is disclosed, for example, in WO91/ available under the name DynaSan 118, 116 and 114 respec 19710. Acid-labile proton pump inhibitors which may be tively). It is also possible if desired for mixtures of triglyc mentioned as particularly preferred are pantoprazole Sodium erides to be present. Sesquihydrate (=pantoprazole Sodiumx1.5H2O), (-)-panto prazole Sodium Sesquihydrate, pantoprazole magnesium 04.04 The fatty acid ester is the ester of an alcohol with dihydrate, omeprazole magnesium, omeprazole and eSome a fatty acid. The alcohol in this case is preferably a linear, prazole. saturated or unsaturated primary alcohol with 10-30, pref erably with 12 to 18, carbon atoms. The fatty acid is 0397. In another prefrred embodiment of the Invention, preferably a monobasic carboxylic acid with 8 to 22, in the active ingredient is a glucocorticosterold, in particular particular 12 to 18, carbon atoms, preferably a naturally cicleSonide. occurring carboxylic acid. Fatty acid esters preferred 0398. The active ingredients may, depending on the according to the invention have a above 30° C. nature of the active ingredient, also be present in the Examples of fatty acid esters which may be mentioned are preparations of the invention in the form of a Salt of the cetyl palmitate, which is commercially available for active ingredient. Particular mention may be made of the example under the name Cutina(E) CP. It is also possible if pharmacologically Suitable Salts of the inorganic and organic desired for mixtures of fatty acid esters to be present. acids normally used in pharmaceutical technology. Suitable 04.05 The Solid paraffin is preferably paraffinum solidum as Such are, on the one hand, water-Soluble and water insoluble acid addition Salts with acids Such as, for example, (ceresin). It is also possible alternatively to use oZokerite, for hydrochloric acid, hydrobromic acid, phosphoric acid, nitric example. It is also possible if desired to use mixtures. acid, Sulfuric acid, , citric acid, D-gluconic acid, 0406. The partial glyceride is according to the Invention benzoic acid, 2-(4-hydroxybenzoyl)benzoic acid, butyric glycerol in which one or two hydroxyl groups are esterified acid, Sulfosalicylic acid, maleic acid, lauric acid, malic acid, by carboxylic acids. The carboxylic acids are preferably fumaric acid, Succinic acid, Oxalic acid, tartaric acid, monobasic carboxylic acids with 8 to 22 carbon atoms, embonic acid, Stearic acid, Sulfonic acid, methane preferably naturally occurring carboxylic acids, in particular Sulfonic acid or 3-hydroxy-2-naphthoic acid, the acids being Stearic acid, palmitic acid and myristic acid. It is possible in employed for preparing the Salts in the equimolar ratio of this case for the carboxylic acids to be different or, prefer amounts, or a ratio differing therefrom, depending on ably, the Same. Examples which may be mentioned are whether the acid is monobasic or polybasic and depending glycerol monoStearate, glycerol distearate and glycerol on which Salt is required. monopalmitate, glycerol dipalmitate. It is also possible if 0399. On the other hand, salts with bases are also suit desired for mixtures of partial glycerides to be present. able. Examples of salts with bases which may be mentioned 04.07 If desired, the mixtures in the individual active are alkali metal (, Sodium, potassium) or calcium, ingredient units may include one or more other pharmaceu aluminum, magnesium, titanium, ammonium, megiumine or tically Suitable excipients. Other Suitable excipients which guanidinium Salts, the bases being employed for preparing may be mentioned by way of example are polymers, Sterols the Salts also in the equimolar ratio of amounts or in a ratio and-in the case of acid-labile active ingredients-basic differing therefrom. compounds. 0400. The skilled worker is aware that active ingredients 04.08 Examples of polymers which may be mentioned and their Salts may, if they are isolated, for example, in are povidone (e.g. Kollidon(R) 17, 30 and 90 from BASF), crystalline form, contain various amounts of Solvents. The Vinylpyrrolidone/vinyl acetate copolymer and polyvinyl active ingredients will therefore also be present in the acetate. Others which may be mentioned are cellulose ethers preparations of the Invention in the form of Solvates and, in Such as, for example, methylcellulose, ethylcellulose (Etho particular, hydrates, and in the form of Solvates and, in cel(R) and hydroxypropylmethylcellulose, cellulose esters particular, also hydrates of the Salts of the active ingredients. Such as cellulose acetate (CAP), cellulose acetate 04.01 The active ingredients may also be chiral com trimellitate (CAT), hydroxypropylmethylcellulose phthalate pounds. It is therefore also possible for the pure enantiomers (HP50 and HP55) or hydroxypropylmethylcellulose acetate of the active ingredients and mixtures thereof in any mixing succinate (HPMCAS)), methacrylic acidimethyl methacry ratio to be present in the preparations of the invention. late copolymer or methacrylic acid/ethyl methacrylate 0402. The fatty alcohol is preferably a linear, Saturated or copolymer (EudragitE L). The polymer is preferably povi unsaturated primary alcohol with 10-30 carbon atoms. It is done or ethylcellulose. It is also possible if desired for preferably a primary alcohol with 10 to 18 carbon atoms in mixtures of polymers to be present. It is possible by adding linear chains. Examples of fatty which may be Suitable polymers, for example, to influence the pharmaceu mentioned are cetyl alcohol, myristyl alcohol, lauryl alcohol tical properties of the individual active ingredient units (e.g. or Stearyl alcohol, with preference for cetyl alcohol. It is also delivery of the active ingredient). Particularly preferred possible if desired for mixtures of fatty alcohols to be polymers according to the invention are povidone or ethyl present. cellulose. US 2004/0058896 A1 Mar. 25, 2004

04.09 The sterol is preferably a or a Zoosterol. larly preferably consist of 0.5 to 15% active ingredient, 15 Examples of which may be mentioned are to 60% solid paraffin, 5 to 50% fatty alcohol, 5 to 10% fatty ergosterol, , Sitosterol, brassicasterol and acid ester and 10 to 50% triglyceride or partial glyceride. . Examples of Zoosterols which may be men 0414. In another embodiment, the invention relates to a tioned are and lanosterol. It is also possible if preparation in which an active ingredient is essentially desired for mixtures of Sterols to be present. uniformly dispersed in an excipient matrix composed of at 0410 Examples of Suitable basic compounds are inor least one fatty alcohol together with at least one excipient ganic basic Salts. Such as ammonium carbonate and Sodium Selected from the group of Solid paraffin or polymer. The carbonate, Salts of fatty acids Such as Sodium Stearate, polymer is preferably ethylcellulose or povidones. Such amines Such as meglumine, di-, triethylamine and TRIS(2- preparations preferably consist of 0.05 to 25% active ingre amino-2-hydroxymethyl-1,3-propanediol) or fatty amines dient, 20 to 90% fatty alcohol, 10 to 80% solid paraffin Such as Stearylamine. Stearylamine and Sodium Stearate may and/or 0.05 to 2% ethylcellulose. Such preparations consist be mentioned as preferred. The addition of basic compounds in particular of 0.1 to 20% active ingredient, 25 to 80% fatty to the mixtures in the individual units results, in the case of alcohol, 10 to 70% solid paraffin and/or 0.1 to 1.5% ethyl acid-labile active ingredients, in particularly stable prepara cellulose. Such preparations particularly preferably consist tions and prevents possible discolorations. of 0.5 to 15% active ingredient, 25 to 70% fatty alcohol, 10 to 60% solid paraffin and/or 0.2 to 1% ethylcellulose. 0411 The proportion (in percent by weight) of active ingredient in the individual active ingredient unit depends on 0415. In the case of acid-labile active ingredients, in the type of active ingredient and is advantageously 0.01 particular the acid-labile proton pump inhibitors, preferred 90%. The proportion of active ingredient is preferably individual active ingredient units of the invention consist of 0.1-70%, particularly preferably 5-40%, in particular 2-70% active ingredient, 10-60% fatty alcohol, 10-60% 10-20%. The proportion of fatty alcohol in the individual solid paraffin, 1-15% polymer and 0.1-2% of a basic com active ingredient unit is advantageously 10-70%, preferably pound. Further preferred individual active ingredient units 20-70%, particularly preferably 20-60% and in particular of the invention consist of 2-70% active ingredient, 10-60% 30-60%. The proportion of triglyceride in the individual triglyceide, 10-60% solid paraffin, 1-15% polymer and 0.1- active ingredient unit is advantageously 10-70%, preferably 2% of a basic compound. Other preferred individual active 20-70%, particularly preferably 20-60% and in particular ingredient units of the Invention consist of 2-70% active 30-60%. The proportion of partial glyceride in the individual ingredient, 10-60% fatty acid ester, 10-60% solid paraffin, active ingredient unit is advantageously 10-70%, preferably 1-15% polymer and 0.1-2% of a basic compound. Particu 20-70%, particularly preferably 20-60% and in particular larly preferred individual active ingredient units of the 30-60%. The proportion of fatty acid ester in the individual Invention consist of 5-40% active ingredient, 20-60% fatty active ingredient unit is advantageously 10-70%, preferably alcohol, 10-60% solid paraffin, 1-15% polymer and 0.1-1% 20-70%, particularly preferably 20-60% and in particular of a basic compound. Further particularly preferred indi 30-60%. The proportion of solid paraffin is advantageously vidual active ingredient units of the invention consist of 10-70%, preferably 20-60% and in particular 30-60%. If 5-40% active ingredient, 20-60% triglyceride, 10-60% solid present, the proportion of polymer in the individual active paraffin, 1-15% polymer and 0.1-1% of a basic compound. ingredient unit is expediently 1-25%, preferably 1-10%, Other particularly preferred individual active ingredient particularly preferably 5-10%. If present, the proportion of units of the invention consist of 5-40% active ingredient, sterol is expediently 1-10%, preferably 1-5%. If present, the 20-60% fatty acid ester, 10-60% solid paraffin, 1-15% proportion of basic compound is 0.05-5%, preferably 0.1- polymer and 0.1-1% of a basic compound. 1%. 0416 Examples of active ingredient units of the inven tion contain 5-40% pantoprazole Sodium Sesquihydrate, 0412 Preferred individual active ingredient units of the 10-40% cetyl alcohol, 5-60% solid paraffin, 1-5% polymer invention consist of 2-70% active ingredient, 10-60% fatty and 0.1-0.2% of a basic compound. Further examples of alcohol, 10-60% solid paraffin and 1-15% polymer. Further active ingredient units of the invention contain 540% pan preferred individual active ingredient units of the invention toprazole Sodium Sesquihydrate, 10-40% glyceryl tripalmi consist of 2-70% active ingredient, 10-60% triglyceride, tate, 5-60% solid paraffin, 1-5% polymer and 0.1-0.2% of a 10-60% solid paraffin, 1-15% polymer. Other preferred basic compound. Other examples of active ingredient units individual active ingredient units of the invention consist of of the invention contain 5-40% pantoprazole Sodium Sesqul 2-70% active ingredient, 10-60% fatty acid ester, 10-60% hydrate, 10-40% glyceryl tripalmitate, 5-60% solid paraffin, solid paraffin and 1-15% polymer. 1-5% polymer and 0.1-0.2% of a basic compound. Still other 0413. In one embodiment, the invention relates to a examples of active ingredient units of the invention contain preparation in which an active ingredient is essentially 10-20% pantoprazole sodium sesquihydrate, 20-40% trig uniformly distributed in an excipient matrix composed of a lyceride, 40-70% solid paraffin, 1-5% sterol and 0.05-0.1% mixture of at least one Solid paraffin, a fatty alcohol, a fatty of a basic compound. acid ester and a partial glyceride or triglycedde. Such 0417. The individual active ingredient units can be pro preparations preferably consist of 0.05 to 25% active ingre duced for example by Spray drying or, preferably, by Spray dient, 10 to 70% solid paraffin, 5 to 80% fatty alcohol, 2 to 20% fatty acid ester and 5 to 80% triglyceride or partial Solidification, in particular also by Spray prilling. Production glyceride. Such preparations consist, in particular, of 0.1 to is particularly preferably by prilling, in particular by Vibra 20% active ingredient, 15 to 65% solid paraffin, 5 to 70% tion prilling. fatty alcohol, 2 to 15% fatty acid ester and 5 to 70% 0418 For the spray solidification or prilling expediently triglyceride or partial glyceride. Such preparations particu the matrix excipients are liquefied to give a melt. The active US 2004/0058896 A1 Mar. 25, 2004 20 ingredient is dissolved or dispersed in this Solution, and the ducing the dosage forms of the invention. Examples which resulting Solution or dispersion is sprayed or, preferably, may be mentioned are dosage forms of the invention, to prilled in a Suitable apparatus. A dispersion of the active which the preparations can be processed, as Suspensions, ingredient in a melt of the exciplents is preferably used. gels, tablets, coated tablets, multicomponent tablets, effer 0419 Spray Solidification takes place in a manner known Vescent tablets, rapidly disintegrating tablets, powders in perse. A detailed description of this technique is to be found Sachets, coated tablets, capsules, Solutions or else Supposi in P. B. Deasy, Microencapsulation and Related Pro tories. Preferred dosage forms in this connection are oral cesses (1984). dosage forms, in particular tablets. Particular preference is 0420. The individual active ingredient units are particu given to rapidly disintegrating tablets and effervescent tab larly preferably produced by Solidification from liquid phase lets. The excipients Suitable for the desired dosage forms are by generating drops by means of vibrating nozzles and by familiar to the skilled worker on the basis of his expert Solidifying the drops which are formed, after they have knowledge. In the case of oral dosage forms it is Surprisingly Stabilized, by drying or cooling in a Suitable medium (pref possible to dispense with the enteric coating. erably gaseous or liquid). The Suitable medium may be, for 0425. In the case of rapidly disintegrating tablets, suitable example, cooled gas Such as air or . Processes of this excipients are, in particular, those excipients which on oral type and corresponding apparatuses are disclosed in DE 27 intake of the bring about rapid disintegration of the 25924, EPO 467 221, WO99/33555 and WO00/24382. tablets. Excipents which on oral intake of the tablet bring 0421. It is particularly preferred according to the inven about rapid disintegration of the tablet preferably comprise tion in the prilling process for the liquid phase flowing to the one or more Substances Selected from the group of fillers and nozzle to be kept at a constant temperature. The Solidifica disintegrants. One or more other excipients from the group tion preferably takes place by instantaneous cooling in a of lubricants, flavors, flavoring Substances and Surface Suitable cooling medium. In prilling, moreover, it is pre active Substances are preferably present in the rapidly dis ferred for the liquid phase flowing to the nozzle, the vibrat ing nozzle and the drops formed by prilling to be kept at a integrating dosage form of the invention. Binders can also be constant temperature until their spherical shape has stabi present if desired. The rapidly disintegrating dosage form lized, and for the Solidification of the drops after their particularly preferably comprises a mixture of at least one Stabilization to be carried out instantaneously by cooling filler, one disintegrant and one lubricant. FillerS Suitable with a gaseous or liquid cooling medium. Systems Suitable according to the invention are, in particular, basic fillerS Such for prilling by means of vibrating nozzles are marketed, for as calcium carbonate (e.g. MagGrandR CC or Destab(R) 95) example, by Brace GmbH, Alzenau, . It is possible and Sodium carbonate, Sugar alcohols such as (e.g. by means of prilling using vibrating nozzles to obtain the Pearlitol(R) or Parteck(R) M), Sorbitol (e.g. Karion(R), xylitol individual active ingredient units in the form of micro or maltitol, Starches Such as corn Starch, potato Starch and Spheres with a narrow monomodal particle Size spectrum in wheat Starch, microcrystalline cellulose, Saccharides Such as the particle size range from 50 um to 2 mm. The narrow , lactose, levulose, and dextrose. In a pre monomodal particle size Spectrum and the uniform Spherical ferred development of the invention, the rapidly disintegrat shape of the microSpheres obtained in this way are expected ing dosage form of the invention comprises as filler a to result in a uniformly Smooth Surface, a uniform, defined mixture of a basic filler (in particular calcium carbonate) and delivery of active ingredient and, in relation to passage a Sugar alcohol (in particular Sorbitol or mannitol). Disin through the Stomach in the case of oral dosage forms (owing tegrants Suitable according to the invention are, in particular, to the small particles), a behavior like that of a solution. The insoluble polyvinylpyrrollidone (insoluble PVP, crospovi microSpheres of the invention are distinguished in particular done), Sodium carboxymethylstarch, Sodium carboxymeth by high Stability, a release of active ingredient which can be ylcellulose, alginic acid and Starches able to carry out the controlled via the particle Size and composition of the function of a disintegrant (e.g. Starch 1500). Suitable lubri matrix, good flow characteristics, good compressibility and cants which may be mentioned are Sodium Stearyl fumarate, a uniform delivery of active ingredient. It is particularly magnesium Stearate, calcium Stearate, Stearic acid, talc and worthy of mention that the microspheres can be further highly disperse Silica (Aerosil). Suitable Surfac-active Sub processed to a large number of pharmaceutical dosage forms stances which may be mentioned are Sodium lauryl Sulfate without thereby losing a given functionality (Such as taste or Tween(R) 20, 60 or 80. Binders suitable according to the masking, resistance to gastric juice, slowing of release). Invention are polyvinylpyrrolidone (PVP, Polyvidon(R) K25, 0422 The microspheres are preferably monomodal 90) or mixtures of PVP with polyvinyl acetate (e.g. Kolli microSpheres with a particle Size range of 50-800 um, don(E) 64), gelatin, corn Starch mucilage, preswollen Starches preferably 50-500 um, particularly preferably 50-400 um, in (Starch 1500), hydroxypropylmethylcellulose (HPMC) or particular 50-200 um. hydroxypropyl-cellulose (L-HPC). 0423. The particle size of the active ingredient employed 0426 The proportion (in percent by weight based on the in the Spray drying or spray Solidification, prilling or vibra finished tablet) of filler in the rapidly disintegrating tablet is tion prilling is advantageously less than or equal to 100 um, advantageously from 1 to 99% by weight. The proportion of in particular less than 40 um. The particle Size is preferably filler is preferably from 30 to 95% by weight, and the in the range 1-20 tim, particularly preferably in the range proportion is very particularly preferably from 60 to 85% by 3-15 lim. Such a particle size can be achieved, for example, weight. by grinding the active ingredient in a Suitable mill. 0427. The proportion (in percent by weight based on the 0424 The individual active ingredient units (prepara finished tablet) of disintegrant in the rapidly disintegrating tions) of the invention can then be used as basis for pro tablet is usually from 1 to 30% by weight. The proportion of US 2004/0058896 A1 Mar. 25, 2004 disintegrant is preferably from 2 to 15% by weight. The of Xanthan, based on the Solution or Suspension ready for proportion of disintegrant is particularly preferably from 5 to use, is usually from 0.1 to 1% by weight. The proportion of 10% by weight. substituted celluloses depends on the viscosity levels of the celluloses and is usually from 0.1 to 10% by weight based 0428 The proportion (in percent by weight based on the on the Solution or Suspension ready for use. Examples of finished tablet) of lubricant in the rapidly disintegrating substituted celluloses of the invention which may be men tablet is usually from 0.1 to 5% by weight. The proportion tioned are carboxymethylcellulose, ethylcellulose or meth of lubricant is preferably from 0.3 to 3% by weight. The ylcellulose or hydroxypropylcellulose. The proportion of proportion of lubricant is particularly preferably from 0.5 to polyvinylpyrrolidone (polyVidone types) is normally from 2% by weight. 0.1 to 10% by weight based on the solution or suspension 0429 The proportion (in percent by weight based on the ready for use. Sheet Silicates Such as the Veegum or bento finished tablet) of individual active ingredient units in the nites can be employed alone or in combination with water rapidly disintegrating tablet is usually from 1 to 90% by soluble thickeners. The total proportion of thickener is then weight. The proportion of individual active ingredient units advantageously from 0.1 to 7% by weight based on the is preferably up to 70% by weight, in particular from 10 to Solution or Suspension ready for use. Alginates and alginic 50% by weight. The proportion is very particularly prefer acid are usually added in a proportion of from 0.1 to 10% by ably from 15 to 25% by weight. weight based on the Solution or Suspension ready for use. Further pharmaceutical excipients preferably employed are 0430. The proportion (in percent by weight based on the insoluble, crosslinked polyvinylpyrrolidone (crospovi finished tablet) of binder can be up to 10% by weight, and dones) and microcrystalline cellulose. It is observed in this it can preferably be up to 5% by weight. case that a loose Sediment forms and prevents agglomeration 0431) If desired, one or more flavoring substances (e.g. of the individual active ingredient units. The ratio of flavors or Sweeteners) can additionally be present in the croSpoVidones to the individual active ingredient units is rapidly disintegrating tablet. This makes it possible, for advantageously from 1:1 to 0.5:1 (based on weight). Micro example, to achieve an improvement of the taste of the crystalline cellulose, which is normally employed in a rapidly disintegrating tablet. These Substances are added in proportion of from 0.5 to 5% by weight based on the solution conventional amounts. or Suspension ready for use, is likewise Suitable for this purpose. The proportion of individual active ingredient units 0432. The rapidly disintegrating tablet is produced by in the Solution or Suspension ready for use is usually processes known to the skilled worker. The rapidly disinte according to the invention from 1 to 20% by weight based grating tablet is preferably produced by on the Solution or Suspension ready for use, preferably 1 to 0433) i) dry mixing of filler and/or disintegrant; 15% by weight and very preferably 5 to 10%. Water is 0434) ii) production of granules of filler and binder and preferably used as Solvent or dispersant for the Solution or mixing of the granules with a disintegrant or Suspension. 0439. Other suitable excipients which may be present in 0435 iii) dry granulation (briqueting or compacting) the Solution or Suspension of the invention are, for example, of one or more excipient components. flavoring Substances (Such as flavors and Sweeteners), buffer 0436 The individual active ingredient units ar Subse Substances, preservatives or else emulsifiers. Flavors are quently admixed to the mixtures obtained in i), ii) or iii) and usually added in a proportion of from 0.05 to 1% by weight. then, if desired, flavorS/flavoring Substances and finally also Other flavoring Substances by way of example are acids Such one or more lubricants are admixed. The mixture obtained in as citric acid, SweetenerS Such as Saccharin, aspartame, this way can be compressed in a tablet preSS under conven cyclamate Sodium or maltol, which are added according to tional conditions. the desired result. Examples of emulsifiers are lecithins, Sodium lauryl Sulfate, TweenSE) or Spans, which are nor 0437. Rapid disintegration of the tablet means according mally added in a proportion of from 0.01 to 1% by weight. to the Invention disintegration of the tablet in about 60 Preservatives Such as benzoic acid, Salts of benzoic acid, Seconds or less when the tablet is Subjected to a disintegra methyl 4-hydroxybenzoate, propyl 4-hydroxybenzoate, Sor tion test as described in the European Pharmacopoeia (3rd bic acid or salts thereof are preferably also added. The edition, 1997) 2.9.1 disintegration time of tablets and cap proportion depends on the preservative used and is normally Sules. from 0.1 to 4% by weight based on the solution or suspen 0438. In the case of Solutions and suspensions, suitable Sion ready for use. excipients are, in particular, those excipients which are 0440 The solution or suspension of the invention is normally used to produce Solutions or Suspensions. Particu produced by techniques known to the Skilled worker. If a larly Suitable according to the invention are excipients with powder for reconstitution is to be produced, preferably a which it is possible to produce a thickened base, Such as mixture of the individual active ingredient units with the thickeners. Examples of thickeners of the invention are thickener and, where appropriate, further excipients is pro Xanthan, Substituted celluloses, polyvinylpyrrolidone (poly duced. This powdered mixture for reconstitution is then Vidone types), sheet Silicates, alginates or alginic acids. Also mixed with a suitable amount of water immediately before possible if desired is a mixture of two or more different administration. Solution or Suspension ready for use is thickeners. The proportion of thickener depends on the normally produced by introducing the individual active desired Viscosity or consistency intended for the Solution or ingredient units into a dispersion of the thickener and, where Suspension ready for use. A Solution or Suspension with a appropriate, of additives in water or, alternatively, by intro viscosity of less than 500 mPas (determined with a rota ducing the thickener into a dispersion of the individual tional Viscometer) is particularly preferred. The proportion active ingredient units in water. US 2004/0058896 A1 Mar. 25, 2004 22

0441. In a preferred embodiment, the invention relates to in the clear melt. At a temperature between 56-60 C., 12.5 rapidly disintegrating tablets or Solutions or Suspension g of pantoprazole Sodium Sesquihydrate is added and Sus which comprise preparations of the invention with PDE pended homogeneously. The Suspension is prilled in the inhibitors as active ingredients. Preferred PDE inhibitors in molten State, and the drops thus produced are Solidified in a this case are roflumilast and pumafentrine. cooling Zone. 0442. The dosage forms of the invention can be Example 6 employed for the treatment and prevention of all diseases which are regarded as treatable or preventable by use of the 0449 47 g of solid paraffin, 40 g of glyceryltripalmitate particular active ingredient. The dosage forms contain the (Dynasan 116, from Hils) and 3 g of sitosterolar converted particular active ingredient in the dose usual for treating the into a clear melt at 100° C. and cooled to 55-60° C. 10 g of particular disease. lansoprazole are added and Suspended homogeneously. The Suspension is put in the feed container of a prilling unit 0443) The production of dosage forms and preparations (from Brace) and prilled from a 200 um nozzle at about 0.1 of the invention is described by way of example below. The bar. A periodic vibration with a frequency of about 390 HZ following examples illustrate the invention in detail without is transmitted to the nozzle head during this. The resulting restricting it. drops are Solidified in a cooling Zone with air at a tempera ture of -30° C. EXAMPLES Example 7 Production of the Preparations (Active Ingredient Units) 0450 15 g of glyceryl trimyristate (Dynasan 114), 15 grams of glyceryl tripalmitate (Dynasan 116), 50 grams of Example 1 Solid paraffin and 5 g of cholesterol are converted into a clear melt at about 100° C. The clear melt is cooled to about 0444 50 g of solid paraffin, 34.9 g of cetyl alcohol and 55-65 C. 15 g of rabeprazole are added, the active ingre 0.1 g of Stearylamine are converted into a clear melt. 5.0 g dient is uniformly dispersed, and the homogeneous Suspen of povidone is dissolved in the clear melt. At a temperature between 56-60C., 10.0 g of pantoprazole sodium sesquihy Sion is priled as in example 6. drate is added and Suspended homogeneously. The Suspen Example 8 Sion is prilled in the molten State, and the drops thus produced are Solidified in a cooling Zone. 0451 10g of glyceryl tripalmitate (Dynasan 116), 209 of glyceryl trimyristate (Dynasan 114), 529 of solid paraffin Example 2 and 3 g of Sitosterol are converted into a clear melt at about 100° C. The clear melt is cooled to 55-65 C. 15 g of 0445. 55 g of solid paraffin, 30.9 g of cetyl alcohol and omeprazole Mg are added and Suspended homogeneously. 0.1 g of Stearylamine are converted into a clear melt. 4.0 g The Suspension is put in the feed container of a prilling unit of povidone is dissolved in the clear melt. At a temperature (from Brace) and prilled through a 200 um nozzle at 90 between 56-60 C., 10.0 g of pantoprazole magnesium is mbar. A periodic vibration with a frequency of about 400 Hz added and Suspended homogeneously. The Suspension is is transmitted to the nozzle head during this. The resulting prilled in the molten State, and the drops thus produced are drops are solidified with air at a temperature of -30° C. in Solidified in a cooling Zone. a cooling Zone. Example 3 Example 9 0446 45.0 g of solid paraffin, 33.8g of cetyl alcohol, 1.0 0452 18 g of tristearin, 60 g of Solid paraffin and 5 g of g off-sitosterol and 0.2 g of Stearylamine are converted into cholesterol are converted into a clear melt. The clear melt is a clear melt. 1.0 g of povidone and 4.0 g of ethylcellulose are cooled to 56-60 C. 10 g of pantoprazole sodium sesquihy dissolved in the clear melt. At a temperature between 56-60 drate are introduced and homogeneously dispersed. The C., 15.0 g of pantoprazole Sodium Sesquihydrate is added Suspension is prilled in the molten State in a prilling unit and Suspended homogeneously. The Suspension is prilled in (from Brace) with vibrating nozzles, and the resulting drops the molten State, and the drops thus produced are Solidified are Solidified in a cooling Zone. in a cooling Zone. Example 10 Example 4 0453 18 g of cetyl palmitate, 40 g of solid paraffin and 2 0447 52.0 g of Solid paraffin, 30.3 g of cetyl alcohol and g of cholesterol are converted into a clear melt. The clear 0.2 g of Stearylamine are converted into a clear melt. 5.0 g melt is cooled to 56-60 C. 10 g of pantoprazole sodium of povidone is dissolved in the clear melt. At a temperature Sesquihydrate are introduced and homogenized until a uni between 56-60C., 12.5g of pantoprazole sodium sesquihy form Suspension results. The Suspension is prilled in the drate is added and Suspended homogeneously. The Suspen molten state in a prilling unit (from Brace) with vibrating Sion is prilled in the molten State, and the drops thus nozzles, and the resulting drops are Solidified in a cooling produced are Solidified in a cooling Zone. ZOC. Example 5 Example 11 0448 77.2 g of cetyl alcohol and 0.3 g of stearylamine are 0454) 50 g of Solid paraffin and 40 g of cetyl palmitate converted into a clear melt. 10.0 g of povidone is dissolved (Cutina(RCP) are converted into a clear melt at 100° C. The US 2004/0058896 A1 Mar. 25, 2004 dear melt is cooled to 50-60C. 10g of pantoprazole sodium Example 18 Sesquihydrate are introduced and Suspended homoge 0461) 90 g of glyceryl monostearate are converted into a neously. The Suspension is prilled in the molten State in a clear melt at about 90° C. 10 g of roflumilast is added, and prilling unit (from Brace) with vibrating nozzles (200 um the mixture is stirred until it is a clear Solution. The clear nozzle), and the resulting drops are Solidified in a cooling melt is prilled at about 70° C. in a suitable vibration prilling ZOC. unit (conditions: 200 or 350 um nozzle, pressure 100 to 170 Example 12 mbar, frequency about 1 kHz). 0455 50 g of Solid paraffin and 40g of cetyl alcohol are Example 19 converted into a clear melt at 100° C. The clear melt is 0462) 88 g of glyceryl myristate and 11.2 g of paraffin are cooled to 50-60 C. 10 g of pantoprazole sodium sesquihy converted into a clear melt at about 90° C. 0.8 g of drate are introduced and Suspended homogeneously. The roflumilast is added, and the mixture is stirred until it is a Suspension is prilled in the molten State in a prilling unit clear Solution. The clear melt is prilled at about 70° C. in a (from Brace) with vibrating nozzles (200 um nozzle), and suitable vibration prilling unit (conditions: 200 or 350 um the resulting drops are Solidified in a cooling Zone. nozzle, pressure 100 to 170 mbar, frequency about 1 kHz). Example 13 Example 20 0456 50 g of solid paraffin and 40 g of glyceryl 0463 96 g of cetyl alcohol and 2 g of ethylcellulose are trimyristate are converted into a clear melt at 100° C. The converted into a clear melt at about 90° C. 2 g of roflumilast clear melt is cooled to 50-60° C. 10 g of pantoprazole is added, and the mixture is stirred until it is a clear Solution. Sodium Sesquihydrate are introduced and Suspended homo The clear melt is prilled at about 70° C. in a suitable geneously. The Suspension is prilled in the molten State in a vibration prilling unit (conditions: 200 or 350 um nozzle, prilling unit (from Brace) with vibrating nozzles (200 um pressure 100 to 170 mbar, frequency about 1 kHz). nozzle), and the resulting drops are Solidified in a cooling ZOC. Example 21 0464 84 g of glyceryl monostearate and 8 g of paraffin Example 14 are converted into a clear melt at about 90° C. 8 g of 0457 47 g of solid paraffin, 40 g of glyceryl tripalmitate roflumilast is added, and the mixture is stirred until it is a (Dynasan 116, from Huls) and 3 g of sitosterol are converted clear Solution. The clear melt is prilled at about 70° C. In a into a clear melt at 100° C. and cooled to 55-60° C. 10 g of suitable vibration prilling unit (conditions: 200 or 350 um lansoprazole are added and Suspended homogeneously. The nozzle, pressure 100 to 170 mbar, frequency about 1 kHz). Suspension is put into the feed container of a prilling unit (from Brace) and prilled from a 200 um nozzle at about 0.1 Example 22 bar. A periodic vibration with a frequency of about 390 HZ 0465 59 g of glyceryl monostearate, 20g of cetyl palmi is transmitted to the nozzle head during this. The resulting tate and 20 g of paraffin are converted into a clear melt at drops are Solidified in a cooling Zone with air at a tempera about 90° C. 1 g of roflumilast is added, and the mixture is ture of -30° C. stirred until it is a dear solution. The clear melt is prilled at about 70° C. in a suitable vibration prilling unit (conditions: Example 15 200 or 350 um nozzle, pressure 100 to 170 mbar, frequency 0458 30 g of tristearin, 60 g of Solid paraffin and 4 g of about 1 kHz). Sitosterol and 0.07 gStearylamine are converted into a clear Example 23 melt. The clear melt is cooled to 56-60 C. 15 g of panto prazole Sodium Sesquihydrate are introduced and homoge 0466 50 g of cetyl alcohol, 5g of glyceryl monostearate, neously dispersed. The Suspension is prilled in the molten 10g of cetyl paimitate, 10 g of glyceryl tristearate and 24.5 State in prilling unit (from Brace) with vibrating nozzles, and g of paraffin are converted into a dear melt at about 90° C. the resulting drops are Solidified in a cooling Zone. 0.5g of roflumilast is added, and the mixture is stirred until it is a clear solution. The clear melt is prilled at about 70° C. Example 16 in a suitable vibration prilling unit (conditions: 200 or 350 lim nozzle, pressure 100 to 170 mbar, frequency about 1 0459 17.5 g of glyceryl trimyristate (Dynasan 114), kHz). 67.59 of Solid paraffin and 5 g of cholesterol are converted into a clear melt at about 100° C. The clear melt is cooled Example 24 to about 55-65 C. 10 g of pantoprazole are added, and the 0467 70 g of cetyl alcohol and 29.5 g of paraffin are active ingredient is uniformly dispersed, and the homoge converted into a clear melt at about 90° C. 0.5 g of neous Suspension is prilled as in example 6. roflumilast is added, and the mixture is stirred until it is a clear solution. The clear melt is prilled at about 75 to 80 C. Example 17 in a suitable vibration prilling unit (conditions: 200 or 350 0460 98 g of cetyl alcohol and 1 g of solid paraffin are lim nozzle, pressure 100 to 170 mbar, frequency about 1 converted into a clear melt at about 90° C. 1 g of roflumilast kHz). is added, and the mixture is stirred until it is a clear Solution. The clear melt is prilled at about 70° C. in a suitable Example 25 vibration prilling unit (conditions: 200 or 350 um nozzle, 0468 97.7 g of cetyl alcohol and 0.3 g of ethylcellulose pressure 100 to 170 mbar, frequency about 1 kHz). are converted into a clear melt at about 90° C. 2 g of US 2004/0058896 A1 Mar. 25, 2004 24 pumafentrine is added, and the mixture is stirred until it is vibration prilling unit (conditions: 100 um nozzle, pressure a clear solution. The clear melt is prilled at about 75 to 80 100 to 170 mbar, frequency about 1.3 kHz). C. in a suitable vibration prilling unit (conditions: 200 or 350 lim nozzle, pressure 100 to 170 mbar, frequency about 1 Example 32 kHz). 0475 36 g of cetyl alcohol, 60 g of glyceryl monostearate and 2 g of vinylpyrollidone/vinyl acetate copolymer and 2 g Example 26 of pumafentrine are converted into a clear melt. The clear 0469 69 g of cetyl alcohol, 5 g of cetyl palmitate, 10 g melt is prilled at about 60° C. with a nozzle and the resulting of glyceryl tristearate and 15 g of paraffin are converted into drops are Solidified by cooling. a clear melt at about 90° C. 1 g of pumafentrine is added, and the mixture is stirred until it is a clear Solution. The clear Example 33 melt is prilled at about 70° C. in a suitable vibration prilling 0476 30 g glyceryl trimyristate, 45g glyceryl monostear unit (conditions: 200 or 350 um nozzle, pressure 100 to 170 ate and 20 g cetyl alcohol are converted into a clear melt. 5 mbar, frequency about 1 kHz). g of roflumilast is added, and homogeneously dispersed. The melt is prilled at about 65 C. and the resulting drops are Example 27 Solidified in cooling Zone. 0470 40 g of cetyl alcohol, 7 g of cetyl palmitate, 33 g of glyceryl tristearate and 15 g of paraffin are converted into Example 34 a clear melt at about 90° C. 5g of (7R,8R,9R)-2,3-dimethyl 0477 80 g cetostearyl alcohol, 0.5 g sodium stearate, 5g 8-hydroxy-7-(2-methoxyethoxy)-9-phenyl-7,8,9,10-tetrahy of Vinylpyrollidone/vinyl acetate copolymer and 12.5g of droimidazol.2-h1,7naphthyridine are added, and the glycerol trimyristate are converted into a clear melt at about mixture is stirred until it is a clear Solution. The clear melt 70° C. 2 g of (7R,8R,9R)-2,3-dimethyl-8-hydroxy-7-(2- is prilled at about 70° C. in a suitable vibration prilling unit methoxyethoxy)-9-phenyl-7,8,9,10-tetrahydroimidazo[1,2- (conditions: 200 or 350 um nozzle, pressure 100 to 170 h1,7naphthyridine is added at 60° C. and dispersed homo mbar, frequency about 1 kHz). geneously. The mixture is prilled at 60° C. and the resulting drops Solidified in a cooling Zone. Example 28 0471. 41 g of cetyl alcohol, 7 g of cetyl palmitate, 33 g Example 35 of glyceryl tristearate and 17 g of paraffin are converted into 0478. 20 g glyceryl trimyristate, 14.5 g. glyceryl a clear melt at about 90° C. 2 g of (7R,8R,9R)-2,3-dimethyl monoStearate, 60 g cetyl alcohol and 5 g Vinylpyrollidone/ 8-hydroxy-7-(2-methoxyethoxy)-9-phenyl-7,8,9,10-tetrahy Vinyl acetate copolymer are converted into a clear melt at droimidazol.2-h1,7naphthyridine are added, and the 70° C. 0.5 g of ciclesonide is added and homogeneously mixture is stirred until it is a clear Solution. The clear melt dispersed. The dear melt is prilled and the resulting drops are is prilled at about 70° C. in a suitable vibration prilling unit Solidified in cooling Zone. (conditions: 200 or 350 um nozzle, pressure 100 to 170 mbar, frequency about 1 kHz). Example 36 Example 29 0479 56.7 g of cetyl alcohol, 3 g of vinylpyrollidone/ Vinyl acetate copolymer, 15 g of Solid paraffin, 15 g of cetyl 0472 41 g of cetyl alcohol, 7 g of cetyl palmitate, 33 g palmitate and 0.1 g of Sodium Stearate are converted into a of glyceryl tristearate and 17 g of paraffin are converted into clear melt. At a temperature between 56-60 C., 10.0 g of a clear melt at about 90° C. 2 g of (7R,8R,9R)-2,3-dimethyl pantoprazole Sodium Sesquihydrate is added and Suspended 8-hydroxy-7-(2-methoxyethoxy)-9-phenyl-7,8,9,10-tetrahy homogeneously. The Suspension is prilled in the molten State droimidazol.2-h1,7naphthyridine are added, and the at 60° C. and the drops thus produced are solidified in a mixture is stirred until it is a clear Solution. The clear melt cooling Zone. is prilled at about 70° C. in a suitable vibration prilling unit (conditions: 200 or 350 um nozzle, pressure 100 to 170 Example 37 mbar, frequency about 1 kHz). 0480 46.7 g of cetostearylic alcohol, 4 g of vinylpyrol Example 30 lidone/vinyl acetate copolymer, 23 g Solid paraffin, 0.3 g of Sodium Stearate and 1 g Sitosterol are converted into a clear 0473 38g of glyceryl tripalmitate, 2 g of cholesterol and melt. At a temperature between 60-65 C. 10.0 g of panto 59.5g of paraffin are converted into a clear melt at about prazole Sodium Sesquihydrate is added and Suspended 100° C. Then 0.5g of ciclesonide is added, and the melt is homogeneously. The Suspension is prilled in the molten State prilled at about 75 C. in a suitable vibration prilling unit at 60 to 65 C. and the drops thus produced are solidified in (conditions: 100 um nozzle, pressure 100 to 170 mbar, a cooling Zone. frequency about 1.3 kHz). Example 38 Example 31 0481 39.9 g of cetyl alcohol, 3 g of vinylpyrollidone/ 0474 38 g of glyceryl tripalmitate, 10 g of cetyl alcohol, Vinyl acetate copolymer, 20 g of cetyl palmitate, 2 g cho 2 g of cholesterol and 49.5g of paraffin are converted into lesterol, 17 g Solid paraffin and 0.1 g of Sodium Stearate are a clear melt at about 100° C. Then 0.5g of ciclesonide is converted into a clear melt. At a temperature between 56-60 added, and the melt is prilled at about 75 C. in a suitable C., 18.0 g of pantoprazole Sodium Sesquihydrate is added US 2004/0058896 A1 Mar. 25, 2004 and Suspended homogeneously. The Suspension is prilled in example 6. The two components are mixed with citric acid the molten state at 60° C. and the drops thus produced are and Sodium carbonate and, after addition of a Suitable Solidified in a cooling Zone. lubricant (for example Sodium Stearyl fumarate) and addi tion of Suitable flavoring Substances, compressed to a tablet. Example 39 0482 47.9 g cetostearylic alcohol, 2 g of vinylpyrolli Example F done/vinyl acetate copolymer, 25g of cetyl palmitate, 1 g 0490 450 mg of Sucrose and 300 mg of Xanthan are Sitosterol, 15 g Solid paraffin and 0.1 g of Sodium Stearate are added to an amount corresponding to 30 mg of rabeprazole converted into a clear melt. At a temperature between 56-60 of the preparation of example 7. The components are mixed, C., 15.0 g of pantoprazole Sodium Sesquihydrate is added and masking flavors are added. The granules are packed into and Suspended homogeneously. The Suspension is prilled in Sachets. The contents of a Sachet can be put into a glass of the molten state at 60° C. and the drops thus produced are water and is ready for use after Stirring. Solidified in a cooling Zone. 0483 The preparations obtained as in examples 1-39 Example G have a particle size in the range 50-700 lum. It is possible, for 0491 60 grams of the preparation of example 8 are mixed example by varying the processing conditions, to obtain dry with 140 grams of mannitol, 30 grams of Kollidon 30 larger particles. and 20 grams of Xanthan. The mixture is granulated with water in a fluidized bed granulator. Granules with a particle 0484 Production of the Dosage Forms size of 0.8-1.5 mm are obtained. The mixture obtained in this Example A way is packed into bags (Sachets). 0485) 134.7 g of mannitol, 30 g of Kollidon(R) 30 and 20 Example H g of Xanthan are mixed dry. The mixture is granulated with water in a fluidized bed granulator. Granules with a particle 0492) 140 g of mannitol, 30 g of Kollidon 30 and 20 g of size of 0.8-1.5 mm are obtained and are mixed with the Xanthan are mixed dry and then granulated with water in a preparation (125 g) obtained as in example 1. The mixture fluidized bed granulator. The resulting granules are obtained in this way is packed into bags (Sachet) or—if Screened. The screen fraction from 0.8 to 1.5 mm is mixed required together with further tablet eXciplents-com with 6.98 g of preparation from example 18 and packed into pressed to tablets in a manner known to the skilled worker. bags (Sachets). Example B Example I 0486 An amount which corresponds to 22.6 mg of pan 0493 5 g of a preparation of example 17 are mixed with toprazole magnesium of the preparation obtained as in 50 g of lactose and 8 g of Xanthan. Sweeteners and flavors example 2 is mixed with 500 mg of lactose and 100 mg of are added to the mixture, and it is packed into bags (Sachets). Xanthan. The mixture is then mixed with flavoring Sub A Suspension ready for drinking is obtained by Stirring a bag stances (Sweetener, flavor) depending on the individual into a glass of water. Sense of taste, and thereafter packed in a bag (Sachet). A Suspension for oral intake is obtained by dissolving the Example J contents of a bag in a glass of water with Stirring. 0494 12.5 mg of a preparation from example 19 are mixed with the appropriate amount of lactose. This mixture Example C is mixed with a mixture of Sodium carbonate and citric acid. 0487. An amount corresponding to 45.2 mg of pantopra After addition of a suitable lubricant (for example sodium Zole Sodium Sesquihydrate of the preparation from example Stearyl fumarate) and addition of flavoring Substances and 3 is mixed with the appropriate amount of lactose. This Sweeteners, the mixture obtained in this way is directly mixture is mixed with a mixture of citric acid and Sodium compressed to an effervescent tablet. Placing the tablet in a carbonate. After addition of a Suitable lubricant (for example glass of water results, after dissolution thereof, in a Suspen Sodium Stearyl fumarate) and addition of one or more Sion ready for drinking. Suitable flavoring Substances, the resulting mixture is com pressed directly (without further granulation) to an efferves Example K cent tablet. A Suspension for oral intake is obtained by 0495 100 mg of a preparation from example 20 are dissolving a tablet in a glass of water. mixed with 1.9 g of lactose and packed into 10 hard gelatin Example D capsules. 0488 An amount corresponding to 45.2 mg of pantopra Example L Zole Sodium Sesquihydrate of the preparation of example 4 is mixed with lactose to improve the flow properties. The 0496 500 mg of a preparation from example 21 are mixture is packed together with Suitable other active ingre granulated with water with 15 g of mannitol and 4 g of dients (for example amoxicillin or NSAIDs in usual dosage Kollidon. The granules sufficient for 100 single doses are forms) into hard gelatin capsules of a Suitable size. packed into capsules. Example E Example M 0489) 300 mg of lactose are added to an amount corre 0497 1 g of a preparation from example 26 are mixed sponding to 30 mg of lanSoprazole of the preparation of with 0.2 g of Xanthan, 0.1 g of Saccharin Sodium, 1.5 g of US 2004/0058896 A1 Mar. 25, 2004 26 mannitol and 0.3 g of dry orange flavor and packed into a Example R Sachet. The suspension after stirring into about 100 ml of 0504) water is ready for use. Example N 1. Preparation from example 22 12.500 mg 0498 200 mg of a preparation from example 27 are 2. Lactose-1-hydrate 49.660 mg 3. Corn starch 13.390 mg mixed with 670 mg of Destab95 SE, 2270 mg of Pearlitol 4. Polyvidon (R) K90 1.300 mg 300 DC and 50 mg of crospovidone in a free-fall mixer. 10 5. Mannit 32.240 mg mg of magnesium Stearate are then added through a Screen. 6. PVP insoluble 12.890 mg 7. Flavors 0.330 mg This mixture is pressed in a tablet press. 8. Magnesium stearate 1.650 mg Example O Total 123.960 mg 0499 40 mg of a preparation from example 30 are mixed with 500 mg of MagGran CC, 200 mg of Karion and 70 mg 0505 Production: 2. and 3. are granulated with a solution of crospoVidone in a free-fall mixer. 12 mg of magnesium of 4. The granules are dried and Screened. 1., 5., 6. and 7. is Stearate are then added through a Screen, followed by brief admixed using a free-fall mixer, and then 8. is briefly mixing again. The mixture obtained in this way is com admixed using a free-fall mixer. The mixture obtained in this pressed in a tablet press. way is compressed in a tablet preSS. Example P Example S 0506) 0500

1. Preparation from example 22 12.500 mg 1. Preparation from example 22 12.500 mg 2. Lactose-1-hydrate 70.300 mg 2. Lactose-1-hydrate 172.125 mg 3. Potatoe starch 19.480 mg 3. Corn starch 45.000 mg 4. Corn starch 2.370 mg 4. Polyvidon (R 25 12.500 mg 5. sodium carboxymethylstarch 1.900 mg 5. Polyvidone insoluble 12.500 mg 6. Flavors 0.330 mg 6. Flavors 2.500 mg 7. Magnesium stearate 0.950 mg 7. Aspartame 0.375 mg Total 105.930 mg 8. Citric acid 2.500 mg 9. Magnesium stearate 2.500 mg Total 262.500 mg 0507 Production: 2. and 3. are granulated with a solution of 4. The granules are dried and Screened. 1., 5. and 6. is admixed using a free-fall mixer, and then 7. is briefly 0501 Production: 2. and 3. are granulated with a solution admixed using a free-fall mixer. The mixture obtained in this of 4. The granules are dried and Screened. 5. is admixed way is compressed in a tablet preSS. using a free-fall mixer, and then 6., 7. and 8. are incorpo rated. 1. is admixed and finally 9. is briefly admixed using 1. A preparation in which an active ingredient is essen a free-fall mixer. The mixture obtained in this way is tially uniformly dispersed in an excipient matrix composed compressed in a tablet preSS. of one or more excipients Selected from the group of fatty alcohol, triglyceride, partial glyceride and fatty acid ester. Example Q 2. A preparation in which an active ingredient is essen tially uniformly dispersed in an excipient matrix composed 0502) of at least one Solid paraffin together with one or more excipients Selected from the group of fatty alcohol, triglyc eride, partial glyceride and fatty acid ester. 1. Preparation from example 23 25.000 mg 3. A preparation in which an active ingredient is i) present 2. Cellactose (R) 229.625 mg in a matrix composed of a mixture comprising at least one 3. Sodium carboxymethylstarch 12.500 mg fatty alcohol and at least one Solid paraffin, ii) present in a 4. Flavors 2.500 mg matrix composed of a mixture comprising at least one 5. Aspartame 0.375 mg triglyceride and at least one Solid paraffin, or iii) present in 6. Citric acid 2.500 mg a matrix composed of a mixture comprising at least one 7. Magnesium stearate 2.500 mg partial glyceride and at least one Solid paraffin or iv) present Total 275,000 mg in a matrix composed of a mixture comprising at least one fatty acid ester and at least one Solid paraffin. 4. A preparation as claimed in claim 1, where the prepa 0503 Production: 2. and 3. are mixed. 4., 5. and 6. are ration is in the form of microSpheres. incorporated. 1. is admixed and finally 9. is briefly admixed 5. A preparation as claimed in claim 4, obtainable by using a free-fall mixer. The mixture obtained in this way is prilling a Solution or dispersion of the active ingredient in compressed in a tablet preSS. the melt of the excipients using a vibrating nozzle. US 2004/0058896 A1 Mar. 25, 2004 27

6. A preparation as claimed in claim 1, where the active 9. A dosage form as claimed in claim 7 in the form of a ingredient is selected from the group of PDE inhibitors, rapidly disintegrating tablet, where the excipients are excipi reversible proton pump inhibitors and glucocorticosteroids. ents which bring about rapid disintegration of Said tablet. 7. A preparation as claimed in claim 1, where one or more 10. A tablet as claimed in claim 9, where in addition one other excipients Selected from the group of polymers and or more excipients from the group of lubricants, flavors, Sterols are present in the preparation. flavoring Substances and Surface-active Substances are 8. A pharmaceutical dosage form comprising a prepara present. tion as claimed in claim 1 together with one or more pharmaceutical excipients.