FAST DISSOLVING COMPOSITION WITH PROLONGED SWEET TASTE

Abstract: A novel fast dissolving pharmaceutical composition in solid dosage form with prolonged sweet taste which comprises (a) at least one pharmaceutically active agent, (b) at least one water soluble sugar, (c) at least one non-sugar sweetener in normal fast release form and (d) at least one non-sugar sweetener in a mucoadhesive slow release form.

Description: FAST DISSOLVING COMPOSITION WITH PROLONGED SWEET TASTE INTRODUCTION The present invention relates to a novel composition of a Fast dissolving Pharmaceutical preparation in solid dosage form with prolonged sweet taste and a process for the manufacture thereof Background of the Invention: Generally, solid pharmaceutical preparation such as tablets/capsules are designed so that after oral administration, they disintegrate or dissolve in the digestive organs and the active ingredients are absorbed Such compositions are not meant to disintegrate or dissolve in the oral cavity However, in certain conditions there is a requirement of fast disintegrating or dissolving tablets which can be administered even without water Such fast dissolving tablets disperse readily to form a suspension or solution of the drug after mixing with the saliva, which is easily swallowed by the patients These are particularly suitable for children or aged patients who have difficulty in chewing and/or swallowing an intact tablet/capsule Fast mouth dissolving tablets are also suitable for those patients - a) Who are suffering from nausea or vomiting b) Who have an upper gastrointestinal tract disease e g , injury in food pipe, c) Who have undergone upper Gl surgery, d) Who are prostrate, e) Who are elderly and have frequent urination problems at night f) Who are incapacitated elderly patients e.g. suffering from Parkinson's disease; g) Who are children; h) Who are in a situation where water is not available. All the above conditions necessitate that solid dosage forms like tablets and capsules should be modiiied to accommodate above conditions. Formulating conventional tablets and liquid dosage forms does not solve all the problems stated above. Dispersible tablets still require water and lead to gritty suspensions. Such reconstituted dosage forms as well as ready-made suspensions still cannot be given in all above conditions and additionally they pose problems of uniformity of doses and stability of the drug. In the past techniques have been reported for producing such fast dissolving tablets, but most of them require the use of highly specialized manufacturing processes or specialized packaging. The Zydis technology from R.P.Scherer, England or instance, utilizes freezedrying of active ingredient with polymer, sugar and other ingredients to form a fast dissolving dosage form.(Manuf. Chemist.Feb.,1990). European Patent Application No. EP 0 839 526 A2 describes the use of a high cost excipient i.e. erythritol in combination with an active ingredient, crystalline Cellulose and disintegrants to prepare fast disintegrating buccal tablets. U.S. Patent No.5, 073, 374 discloses a fast dissolving buccal tablet containing an active ingredient, a water soluble sugar such as sorbitol and a lubricant. U.S. Patent No.5, 085, 876 discloses a surprisingly fast dissolving sweetening agent in combination with caramel. US Patent No. 5,466,464 discloses a solid preparation soluble in buccal cavity containing agar in combination with sugars like lactose and/or mannitol and an active ingredient. The drawback in this preparation is that agar is a natural material susceptible to variability and microbial contamination. The composition described in U.S. Patent No.5,720,974 requires a special "Compression-Molding" process to produce fast dissolving tablet. U.S. Patent No.5,837,285 discloses fast soluble tablets which are produced by a novel process which involves the compression shaping of a wet kneaded mass of drug and sugar alcohol. The wet tablets produced are thereafter dried. Another US Patent No 5,869,098 discloses fast dissolving compressed tablets manufactured by using partially hygroscopic shearform matrices Such matrices are prepared from sugar carriers using a flash-heat process Further U S Patent No 5, 112616 discloses the use of solid selected from polyethylene glycols and glycerides, which glyceπdes melt in the range of 25°C to 45°C surfactants selected from the groups consisting of nonionic Poly (oxypropylene)Poly (oxethylene) copolymers, polyoxyethylene polysorbate derivatives and sodium lauryl sulfate to prepare fast dissolving buccal tablets PCT Application Number WO 93/23017 defines a fast dissolving matrix consisting of gelatin, pectin and /or soy fiber protein and one or more ammo acids having from 2 to 12 carbon atoms All the compositions disclosed in the prior art suffer from the drawback of a bitter taste in the mouth after consumption and also do not provide for a prolonged sweet taste in oral cavity after consumption of such fast dissolving compositions It is the object of the present invention to provide a pharmaceutical preparation in solid dosage form, preferably in the form of a compressed tablet which when orally administered dissolves or disperses in the mouth within one minute requiring very little amount of body fluids like saliva to produce a smooth solution or suspension of the drug with a prolonged sweet taste Accordingly the present invention relates to a novel fast dissolving pharmaceutical composition in solid dosage form with prolonged sweet taste which comprises a) At least one pharmaceutically active agent from 0 1 to 99 weight % b) At least one water soluble sugar, such as herein described, in an amount of from 5 to 95 weight % of the total dosage form c) At least one non-sugar sweetner, such as herein described, in their normal fast release form in an amount of from 0 to 10 weight % of the total dosage form d) At least one non-sugar sweetner, such as herein described, in a mucoadhesive slow release form obtained as herein described in an amount of from 0 5 to 20 weight % of the total dosage form The present invention also relates to a process for the preparation of a novel fast dissolving pharmaceutical composition in solid dosage form with prolonged sweet taste which comprises mixing the following ingredients a) At least one pharmaceutically active agent from 0 1 to 99 weight % of the total form b) At least one water soluble sugar, such as herein described, in an amount of form5 to 95 weight % of the total dosage form c) At least one non-sugar sweetner.such as herein described, in their normal fast release form in an amount of from 0 to 10 weight % of the total dosage form d) At least one non-sugar sweetner, such as herein described, in a mucoadhesive slow release form obtained as herein described in an amount of from 0 5 to 20 weight % of the total dosage form and compressing the resulting mixture obtained into tablets or any other solid dosage form The water soluble sugars which can be used in the process according to the present invention are Mannιtol,Sorbιtol,Xylιtol and the like The non-sugar sweetners which can be used in the process according to the present invention are Aspartame.Acesulfame potassium, Saccharin sodium, Cyclamates.Glycirrhizin and the like The non-sugar sweetner in a mucoadhesive slow release form is obtained by mixing coating, granulating, encapsulation, matrix formulation or complexation a non-sugar sweetner with a mucoadhesive agent as stated herein The drugs pharmaceutical agents or their salts to be employed for the fast dissolving buccal tablet in accordance with the present invention can be selected from the following group of drugs- α-ADRENERGIC AGONIST such as Adrafinil, Adrenolone, Amidephnne, Apraclonidine, Budralazine, Clonidine, Cyclopentamine, Detomidine, Dimetofπne, Dipivefrin, Ephedπne, Epinephnne, Fenoxazoline, Guanbenz.Guanafacine, Hydroxyamphetamine, Ibopamine, Indanazoiine, Isometheptene, Mephentermine, Metaraminol, Methoxamine, Methylhexaneamine, Metizolene, Midodπne, Naphazohne, Norepinephnne, Norfenefππe, Octodπne, Octopamine, Oxymetazolιne,Phenylephrιne,Phenylpropanolamιne,Phenylpropymethylamιne, Pholedπne.Propylhexedrine, Pseudoephredπne, Rilmenedine.Synephnne, Tetrahydrozoline, Tiamenidine.Tramazo ne, Tuaminoheptane Tymazo ne Tyramine.Xylometazohne β-ADRENERGIC AGONIST such as Formoterol, Methoxyphenamine Ritodπne.Terbuterol α-ARENERGIC BLO ER such as Dapiprazole, Doxazosin, Ergoloid, Mesylates,Fenspιπde,Parazosιn,Tarazosιn,Tolazolιne Yohimbine α-ADRENERGIC BLOCKER such as Acebutolol, Amosulalol, Arotinolol, Atenolol, Befunolol, Betaxolol, Bevantolol, Bisoprolol Bopindolol, Bucumolol Bufetolol, Buforalol Bunitrolol, Bupranolol, Butofilolol, Carazolol, Carteolol, Carvedilol Celiprolol Cetamolol,Cloranolol,Dιlevalol, Epanolol, Esmolol, Indenolol, Labetalol, Levobunolol Mepindolol, Metipranolo, Metoprolol.Moprolol, Nadolol, Nadoxolol, Nifenalol, Nιpradιlol,Oxprenolol, Penbutolol, Pindolol, Practolol, Propranolol, Sotalol, Sulfinalol, Talιnolol,Tertatolol, Timolol, Toliprolol, Xibenolol ALCOHOL DETERRENT such as calcium cyanamide citrated, Disulfiram, Nitrefazole ALDOSE REDUCTASE INHIBITOR such as Epalrestat, Ponalrestat, Sorbinil, Tolrestat ANABOLIC such as Androιsoxazole,Androstenedιol, Bolandiol, Bolasterone, Clostebol, Ethylestrenol, Formyldienolone, 4-Hydroxy-19-nortestosterone, Methandnol Methenolone, Methltπenolone, Nandrolone, Decanoate, Nandrolone-Hexyloxyphenyl- propionate, Nandrolone Phenpropionate, Norbolethone, Oxymesterone, Quinbolone, Stenbolone, Trenbolone, ANALGESIC (DENTAL) such as Chlorobutanol, Clove Eugenol, Potassium Nitrate, Potassium Oxalate ANALGESIC (NARCOTIC) such as Alfentanil, Allylprodine, Alphaprodine, Anileridine, Benzylmorphine, Bezitramide, Buprenorphine, Butorphanol, Clonitazene, Codeines, Desomorphine, Dextromoramide, Dezocme, Diampromide, Dihydrocodeine, Dihydrocodeineone Enol Acetate, Dihydromorphine, Dimenoxadole, Dimepheptanol, Dimethylthiambutene, Dioxaphetyl, Butyrate, Dipipanone, Eptazocine, Ethoheptazine, Ethylmethlythiambutene, Ethylmorphme, Etonitazine, Fentanyl, Hydrocodone, Hydromorphone, Hydroxypethidme, Isomethadone, Ketobemidone, Levorphanol, Lofentanil, Mepeπdine, Meptazinol, etazocine, Methadone, Metopon, Morphine, Morphine Derivatives, Myrophine, nalbuphine, Narceine, Nicomorphme, Norlevorphanol, Normethadone, Normorphine, Norpipanone, Opium, Oxycodone, Oxymorphone, Papaveretum, Pentazocine, Phenadoxone, Phenazocine, Pheopeπdine, Piminodine, Piπtramide, Proheptazine Promedol, Propeπdine, Propiram, Propoxyphene, Sufentanil, Tihdine ANALGESIC (NON-NARCOTIC) such as Acetaminophene, Acetaminosalol, Acetanihde, Acetylsalicylates, Acetylsalicylsalicy c Acid, Alclofenac, Alminoprofen, Aloxipπn, Aluminium Bis (acetylsa cylate), Aminochlorthenoxazine, 2-Amιno-4-pιcolιne, Aminopropy'on, Aminopyπn, Antipynne, Antipyπne Salicylate, Antrafenine Apazone, Aspirin Benorylate, Benoxaprofen, Benzpiperylon, Benzydamine, p-Bromoacetanilide, 5-Bromosalιcylιc Acid Acetate, Bufexamac, Bucetin, Bumadizone, Butacetin, Carbamazepine, Carbetidine, Carbiphene, Carsalam, Chloralantipyπne, Chlorthenoxazιn(e), Cholin, Salicylate, Cmchophene, Ciramadol, Clometacm, Cropropamide, Crotethamide, Dexoxadrol, Difenamizole, Diflunisal, Dipyrocetyl, Dipyrone, Emorfazone, Enfenamic Acid, Epiπzole, Etersalate, Ethenzamide, Ethoxazene, Etodolac, Felbinac, Fenoprofen, Floctafenine, Flufenamic Acid, Fluroesone, Flupirtine, Fluproquazone, Flurbiprofen, Fosfosal, Gentisic Acid, Glafenine, Ibufenac, Imidazole Salicylate, Indomethacin, Indoprofen, Isofezolac, Isoladole, Isonixine, Ketoprofen Ketotolac, p-Lactophenetide, Lefetamine, Loxoprofen Lysme Acetylsahcylate, Methotπmeprazine, Metofohne, Miroprofen, Moraone, Morphohne Salicylate, Naproxen, Nefopam, Nifenazone, 5' Nιtro-2'Propoxyacetanιlιde, Parsalmide, Pensoxal, Phenacetin, Phenazopyndine, Phenocoll, Phenopyrazone, Phenyl Acetylsahcylate, Phenyl salicylate, Phenyramidol, Pipebuzone, Piperylone, Prodi dine, Propacetamol, Propyphenazone, Proxazole, Quinine Salicylate, Ramifenazone, Rimazolium.metilsulfate, Salacetamide, salicin, Salicyamide, O-Acetic Acid, Salicylic Acid.Sa cylates and derivatives, Salicylsulfunc Acid, Salsalte, Salvenne, Simetπde, Sulfamipyπne, Suprofen, Talniflumate, Tenoxicam, Terofenamate, Tetradπne.Tinoπdine, Tolfenamic Acid, Tolpronine, Tramadol, Viminol, Xenbucin, Zomepirac ANDROZEN such as Boldenone, Fluoxymesterone, Mestaπolone, Mesterolone, Methandrostenolone, 17-Methyιtestoserone, 17α -Methyl-testosterone 3- cyclopentyl Enol Ether, Norethandrolone, Normethandrone, Oxandrolone, Oxymetholone, Prasterone, Stanlolone, Stanozolol, Testosterone, Testosterone 17 - Chloral Hemiacetal, Testosterone 17-βcypιonate, Testosterone Enanthate, Testosterone, Nicotinate, Testosterone Phenylnylacetate, Testosterone Propionate, Tiomesterone, ANESTHETIC such as Acetamidoeugenol, Alfadolone, Acetate Alfaxalone Amucaine Amolanone.Amylocaine.Benoxinate, Betoxycaine, Biphenamine, Bupivacaine, Burethamine, Butacaine, Butaben, Butani caine, Buthalital, Butoxycaine, Carticaine, 2- Chloroprocain, Cocaethylene, Cocaine, Cyclomethycaine, Cocaethylene, Dibucaine, Dimethisoquin, Dimethocaine, Diperadone, Dyclonine, Ecgonidine, Ecgonine, Ethyl Aminobenzoate, Ethyl Chloride, Etidocaine, Etoxadrol, β -Eucaine, Euprocin, Fenalcomine, Femocaine, Hexobarbital, Hexylcaine Hydroxydione, Hydroxyprocaine Hydroxytetracaine, Isobutyl p- Aminobenzoate, Kentamine, Leucinocaine Mesylate, Levoxadrol, Lidocaine.Mepivacaine, Meprylcaine, Metabutoxycaine, Methohexital, Methyl Chloride, Midazolam, Myrtecaine, Naepaine, Octacaine, Orthocaιne,Oxethazaιne, Parethoxycaine, Phenacaine, Phencylidiπe, Phenol Piperocaine, Pindocaine, Po docanol, Pramoxine, Pπlocaine, Procaine, Propanidid, Propanocaine, Proparacaine, Propipocaine, Propofol, Propoxycaine, Psedococaine Pyrocaine, Risocaine, Salicyl Alcohol, Tetracaine, Thialbarbital, Thimylal, Thiobutabarbital, Thiopental, Tolycaine, Tπmecaine, Zolamine ANOREXIC such as Aminorex, Amphecloral, Benzaphetamine, Chlorphentermine, Clobenzorax, Chloforex, Cyclexedπne, Diphemethoxidine.Fenbutrazate, Fenfluramine, Fenproporex, Furfurylmethylamphetamine, Levophacetoperate, Mefenorex, Metamfeproamone, Norpseudoephedπne, Phenpetermine, Picilorex ANTHELMINTIC (CESTODES) such as Arecoline, Aspidine, Aspidinol, Dιchlorophen(e), Embelin, Kosin, Napthalene, Niclosamide, Pellertienne, Pellertienne Tannate, Quinacπne Anthelmintic (NEMATODES) such as Alantolactone, Amoscanate, Ascandole Bephenium, Bitoscanate, Carbon Tetrachlonde, Carvacrol, Cyclobendazole Diethylcarbamazine, Diphenane, Dithiazanine Iodide, Dymanthine, Gentian Violet, 4- Hexylresorcinol, Kainic Acid, Mebendazole, 2- Napthol, Oxantel, Piperazines, Pyrantel, Pyrvinium Pamoate, α-Santonin, Stilbazium Iodide, Tetrachloroethylene Thiabendazole, Thymol, Thymyl Nsoamylcarbamate, Tnchlofenol Piperazine, Urea Stibamine ANTHELMINTIC (ONCHOCERCA) such as Ivermectin ANTHELMINTIC (SCHISTOSOMA) such as Amphotalide, Antιmoπy(s) and Derivatives Becanthone, Hycanthone, Lucanthone, Niπdazole, Oxaminquine, Praziquantel, Stibocaptate, Stibophen ANTHELMINTIC (TREMATODES) such as Anthiolimine ANTIACNE such as Algestone, Acetophenide, Azelaic Acid, Benzoyl Peroxide Dichloroacetic acid, Motretinide, Retinoic Acid, Tetroquinone ANTIALLERGIC such as Amlexanox, Astimizole, Azelastine, Cromolyn, Fenpiprane, Histamines, Ketotifen, Nedocromil, Oxatomide, Pentigetide, Poison Ivy Extract, Poison Oak Extract, Poison Sumac Extract, Repinnast, Tiaramide, Tranilast, Traxanox, Urushiol, Cetinzine, Fexophenadine ANTIAMEBIC such as Arsthinol, Bialamicol, Carbarsone, Cephaehne, Chlorbetamide Chlorphenoxamide, Dehydroemetine, Dibromopropamidine, Diloxanide, Dephetarsone Emetine, Fumagil n, Glaucarubin, Glycobiarsol, 8-Hydroxy-7-ιodo-5-quιnolιnesfulfonιc Acid, lodochlorhydroxyquin, lodoquinol, Paromomycin, Phanquinone, Phearsone Sulfoxylate, Polybenzarsol, Propamidine, Quinfamide, Secnidazole, Sulfarside Techlozan, Thiocarbamizine, Thiocarbasone, Tinidazole ANTIANDROGEN such as Bifluranol, Cyoctol, Cyproterone, Oxendolone ANTIANGINAL such as Amlodipine, Amyl Nitrate, Cinepazet Maleate, Imolamine, Isosorbide Dinitrate, Limaprost, Molsidomine, Nitroxyalklamide Derivatives ANTIARRHYTHMIC such as Acecaine, Adenosine, Ajma ne, Alprenolol, S-Aminoalkyl- s-Arylsulfoximines, Amoproxan, Aprindine, Bretylium Tosylate, Bubumolol, Bunaftine Butidnne, Butobendine, Capobenic Acid, Cifen ne, Disopyramide, Encainide Flecainide, Hydroquinidine, Indecainide, Ipratopium, Lorajmine, Lorcainide, Meobentine Mexiletine, Monciziπe, Pirmenol, Prajmahne, Procainamide, Pronethalol, Propafenone Pyπno ne Quinidine.Quinidine Sulfate Quinidine, Tocainide, Viquidil ANTIARTERIOSCLEROTIC such as Pyπdinol Carbamate ANTIARTHRITIC/ANTIRHEUMATIC such as Allocupreide Sodium, Auranofin Aurothioglucose, Aurothioglycanide, Azathiopπne, D-tert-Butyl-phenols, Calcium 3- Aurothιo-2-propanol-1-sulfonate, Clobuzant, Cuproxoline, Diacerein, Glucosamine, Gold Sodium TThiosulfate Hydroxychloroquine, Kebuzone Lobenzaπt, Melittin Myoral Penicillamine ANTIBACTERIAL (ANTIBIOTIC) Aminoglycosides such as Amikacin, Apramycin, Arbekacin, Bambermycins Butirosin Dibekacin Dihrostreptomycin Fortιmιcιn(s), Fradiomycin Geπtamicin, Ispamicin kanamycin Micronomicin, Neomycin, Neomycin Undecylenate Netilmicin Paromomycin.Ribostamycin, Sisomycin, Spectinomycin, Streptomycin, Streptonicozid Tobramycin Amphenicols such as Azidamfenicol, Chloramphenicol, Chloramphenicol Palmirate Chloramphenicol Pantothenate, Florfenicol, Thiamphenicol, Ansamycins such as Rifamide, Rifampin, Rifamycin Rifaximin, Rifapentene β-Lactams Carbapenems such as Imipenem Cephalospoπns, such as 1 -Carba(dethιa)Cephalospoπn, Cefactor, Cefadroxil, Cephalospoπns, Cefatnzine, Cefazedone, Cefazo n, Cefexime, Cefmenoxime, Cefodizime, Cefonicid, Cefoperazone, Ceforanide.Cefotaxime, Cefotiam, Cefmizole Cefpinmide, Cefpodoxime Proxetil, Cefroxadine, Cefsulodin.Ceftazidime, Cefteram, Ceftezole, Ceftibuten, Ceftizoxime, Ceftnaxone, Cefuroxime, Cefuzonam, Cephacetπle, Sodium, Cephalexin, Cephaloglycin.Cephalondine, Cephalosponn, Cephalothin Cephapinn, Sodium, Cephradine, Pivcefalexine Cephamycin such as Cefbuperazone, Cefmetazole, Cefminox, Cefetan, Cefoxitin Manobactams such as Aztreonam caru onam, Tigemonam Oxacephems such as Flomoxef, Moxolactam Penicillins such as Amidinocillin, Amdinocillin, Pivoxil, Amoxicillin, Ampicillan, Apalcil n Aspoxicil n, Azidocillan, Azlocillan, Bacampicillin, Benzylpenicillinic Acid, Benzylpenicil n, Carbenicillin, Carefecillin, Carindacillin, Clometocillin, Cloxacillin Cyclacillin, Dicloxacillin, Diphenicil n, Epicil n, Fenbenicil n, Floxicil n, Hetacillin Lenampicillin, Metampicil n, Methicillin, Mezlocillin, Nafcillin, Oxacil n, Penamecillin, Penethamate Hydriodide, Penicillin G Benethamine, Penicillin G Benzathine Penicillin G Benzhydrylamine, Penicillin G Calcium, Penicillin G Hydrabamine, Penicillin G Potassium, Penicillin G Procaine, Penicillin N, Penicillin 0, Penicillin V, Penicillin V Benzathine, Penicillin V Hydrabamine, Penimepicyc ne, Phenethici n, Piperacillin Pivapicillin, Propicil n, Quinacillin, Sulbencillin, Talampιcιllιn,Temocιl n, Ticarcillin Lincosamides such as clindamycin, Lincomycin Macrolides such as Azithromycin, Carbomycin, Claπthromycin, Erythomycιn(s) and Derivatives, Josamycin, Leucomycins, Midecamycins, Miokamycin, Oleandomycin, Pnmycin, Rosaramicin, Roxithromycin, Spiramycin, Troleandomycin Polypeptides such as Amphomycin, Bacitracin, Capreomycin, Colistin, Enduracidin, Enviomycin, Fusafungine, Gramιcιdιn(s), Gramicidin S, Mikamycin, Polymyxin Polymyxin B- Methanesulfonic, Acid, Pπtinamycin Ristocetin, Teicoplaπin, Thiostrepton Tuberactinomycin, Tyrocidine, Tyrothncin, Vancomycin, Vιmomycιn(s), Virginiamycin Zinc Bacitracin Tetracyclines such as Apicycline, Chlortetracycline, Clomocycline, Demeclocycline Guamecycline, Lymecycline, Meclocychne, Methacycline, Minocychne, Oxytetracyhne, Penimepicycline, Pipacychne, Rohtetracycline, Sancyc ne, Senociclin, Tetracycline Others such as Cyclosenne, Mupirocin, Tuberin ANTIBACTERIAL (SYNTHETIC) 2,4-Dιamιnopyrιmιdιes such as Brodimopπm, Tetroxopπm, Tπmethopπm Nitrofurans such as Furaltadone, Furazolium, Nifuradene, Nifuratel, Nifurfoline, Nifurpinnol, Nifurprazine, Nifurtoinol, Nitrofurantoin Quinolones and Analogs such as Amifloxacin, Cinoxacin, Ciprofloxacm, Difloxacin, Enoxacin, Fleroxacin, Flumequine, Lomefloxacin, Miloxacin, Nalidixic Acid, Norfloxacin, Ofloxacin, Oxolinic, Acid, Pefloxacin, Pipemidic Acid, Piromidic Acid, Rosoxacin, Temafloxacin Sulfonamides such as Acetyl Sulfamethoxypyrazine, Acetyl Sulfisoxazole Azosulfamide, Benzylsulfamide, Chloramine-B, Chloramine-T, DichloramineT 4 Formosulfathiazole, N -Formyl-Sulfisomidine, N -β-D- Glucosysulfanilamide, Mafenide 4'-(Methyl-sulfamoyl) sulfanilanilide, p-Nitrosulfathiazole, Noprysulfamide Phthalysulfacetamide, Phthalysulfathiazole, Salazosufadimidine, Succinylsulfathiazole, Sulfabenzamide, Sulfacetamide Sulfachlorpyπdazine, Sulfachrysoidine, Sulfacytine, Sulfadiazine, Suifadicramide, Sulfadimethoxine, Sulfadoxine, Sulfaethidole Sulfaguanidine, ^ Sulfaguanol, Sulfalene, Sulfaloxic Acid, Sulfamerazine, Sulfameter.Sulfamethazine, Sulfamethizole, Sulfamethomidine, Sulfamethoxazole, Sulfamethoxypyπdazine, Sulfametrole, Sulfamidochrysoidine, Sulfamoxole.Sulfanilamide, Sulfanilamidomethanesulfonic Acid, Tnethnolamine Salt, 4- Sulfanilamidosalycy Acid, N 4 -SulfanιlySulfanιlamιde, Sulfanilyurea, N-Sulfanιlyl-3,4- xylamide, Sulfanitran, Sulfapenne, Sulfaphenazole, Sulfaproxylιne,Sulfapyrazιne, Sulfapindine, Sulfasomizole, Sulfasymazine.Sulfathiozole, Sulfathiourea, Sulfatolamide, Sulfisomidine, Sulfisoxazole Sulfones Such as Acedapsone, Acediasulfone, Acetosulfone, Dapsone, Diathimosulfone, Glocosulfone, Solasulfone, Succisulfone, Sulfanilic Acid, p- sulfanilyibenzyllamine, p p-sulfonyldιanιlιne,-N,N'dιgalactosιde, Sulfoxone, Thiazolesulfone Others such as Clofoctol, Hexedine, Magainis, Methenamine Anhydromethylenecitrate, Methenamine Hippurate, Methenamine Mandelate, Methenamine Sulfosa cylate, Nitroxohne, Squalamine, Xibornol ANTICHOLINERGIC Such as Adiphenine, Alvenne, Ambutonomium, Aminopentamide, Amixetnne, Amprotropine, Phosphate, Anisotropine, Methylbromide, Apoatropine, Atropine, Atropine N-Oxide, Benactyzine.Benapryzine Benzetimide, Benzelonium Benztropine, Mesylate, Bevonium Methyl Sulfate Bipe den Butropium N-Butylscopolammonium Bromide Buzepide, Camylofine, Caramiphen Chlorbenzoxamine, Chlorphenoxamine, Cimetropium, Clidinium.Cyclodπne, Cyclonium, Cyclopentolate, Cycrimine.Deptropine, Dexitimide, Dibutohne Sulfate, Dicyclomine Diethazine, Difemerine, Dihexyveπne, Diphemanil, Methylsulfate, N-(1 ,2- Dιpheylethyl)nιcotιnamιde, Dipiprovnne, Diponium, Emepronium, Endobenzylme Ethopropazine, Ethybenztropine, Ethylbenzhydramine, Etomido ne, Eucatropine, Fenpiveπnium, Fentonium, Flutropium Glycopyrrolate, Heteronium Hexocyc um Methyl Sulfate, Homatropine, Homatropine Methyl Bromide, Hyoscymamiπe, Ipratropium Isopropamide, Levomepate, Meceoxamine, Mepenzolate, Metcaraphen, Methantheline, Methixene, Methscopolamine, Octamylamine, Oxybutynin, Oxyphencyclimine, Oxyphenonium, Pentapipeπde, Penthienate, Phencarbamide, Phenglutaπmide Pipenzolate, Pipeπdolate, Pipeπlate, Poldine Methysulfate, Pndinol, Pr finium, Propyromazine, Scopolamine N-Oxide, Stilonium, Stramonium, Sultroponium, Thihexinol, Thiphenamil, Tiemonium, Timepidium, Tiquizium, Tridihexethyl Iodide, Tnhexyphenidyl, Hydrochloride, Tropacine, Tropenzile, Tropicamide, Trospium, Valethamate, Xenytropium ANTICONVULSANT Such as Acetylphenetunde, Albutoin, Aloxidone, Aminoglutethimide, 4-Amιno-3-Hydroxybutyπc Acid, Atrolactamide, Beclamide, Buramate, Carbamazepine, Cinromide, Clonazepam, Decimemide, Diethadione Dimethadione, Doxenitoin, Eterobarb, Ethadione, Ethosuximide, Ethotoin, Fluresone 5-Hydroxytryptophan, Lamotngine, Magnesium Sulfate, Mephenytoin, Metharbital, Methetoin, Methsuximide, 5-Methyl-5-(3-phenanthryl)-hydantoιn, 3-Methyl-5- Phenylhydantoin, Narcobarbital, Nimetazepam, Nitrazepam, Paramethadione, Phenacemide, Phenetunde, Phensuximide, Phenytoin, Phethenylate Sodium, Pπmidone, Progabide, Solanum, Strontium, Suclofenide, Sulthiame, Tetrantoin, Tπmethadione, Valproic Acide, Valpromide, Vigabatπne, Zomsamide ANTIDEPRESSANT Bicyclics such as Binedaline, Caroxazone, Citalopram, Dimethazan Indalpine fencamine, Indeloxazine, Nefopam, Nomifensine, Oxitnptan, Oxypertine, Paroxetine Sertrahne, Thiazesim, Trazodone, Zometapine, Hydrazides/Hydrazines such as Benmoxine, Iproclozide, Iproniazid, Isocarboxazid Nialamide, lctamoxine, Phenelzine Pyrrolidones such as Continine, Rolicypnne, Rolipram Tetracychcs such as Maprotihne, Metrahndole, Miansenne, Oxaproti ne Tricyc cs such as Adinazolam, Amitπptyline, Amitπptylinoxide, Amoxapine, Butnptyline Clomiparamine, Demexiptiline, desiparamine, Dibenzepin, Dimetracrine, Dothiepin Doxepin, Fluacizine, Imipramine, Imipramine N-Oxide, Iprindole, Lofepramine, Me tracen, Metapramine, Nortriptyline, Noxipti n, Opipramol, Propizepine, Protπptyline Quinupramine, Tianeptine, trimiparamine Others such as Benactyzine, Bupropin, Butacetin, Deanol, Deanol Aceglumate, Deanol Acetamidebenzoate, Dioxadrol, etopendone, Febarbamate, Femoxetine, Fenpentadiole, Fluoxetine, Fluvoxamine, Hematopotphyrin, Hypercinin, Levophacetoperane, Lithium Medifoxamine, Minapnne, Moclobemide, Oxaflozane, Piberaline, Polycyc c Imides, Pro ntane, Pyπsuccideanol, Rubidium, Sulpiπde, Sultopπde, Teniloxazine, Thoza none, Tofenacin, Toloxatone, Tranylcypromine, L-Tryptophan, Viloxazine, Zimeldine ANTIDIABETIC Biguanides such as Buformine, Metformin, Phenformin Sulfontlurea Derivatives such as Acetohexamide, 1 -Butyl-3-metanιlylurea, Carbutamide Chlorpropamide, Glibomuride, Gliclazide, G pizide, G quidone, G soxepid, Glybunde, Glybuthιazol(e), Glybuzole, Glyhexamide, Glymidine, Glypinamide, Phenbutamide, Tolazamide, Tolbutamide Tolcyclamide Others such as Acarbose, Benzylthιazolldone-2,4-dιone, Calcium Mesoxalate, Miglitol ANTIDIARRHEAL such as Acetyltannic Acid, Albumin Tannate, Alkofanone, Aluminium Sa cylates, Catechin, Difenoxin, diphenoxylate, Lidamidine, Loperamide, Mebiquine Trillium, Uzaπn ANTIDIURETIC such as Desmopressin felypressin, Lypressin, Ornipressin Oxcinchophen, Terlipressin, Vasopressin ANTIESTROGEN such as Delmadione Acetate, Ethamoxytπphetol, Tamoxifen Toremifene ATRIFUNGAL (ANTIBIOTICS) Polyenes such as Amphoteπcin-B.Canadicidin, Dermostatin, Filpin, Fungichromin, Hachιmycιn,Hamycιn, Lucensomycin, Mepartπcin, Natamycin, Nystatιn,Pecιlocιn,Perιmycιn Others such as Azasenne, Griseofulvin, Oligomycins, Pyrrolnitnn, Siccanin, Tubercidin.Viridin. ANTIFUNGAL (SYNTHETIC) Allylamines such as Naftifine, Tebinafine Imidazoles such as Bifonazole, Butoconazole, Chlordantoin, Chlormidazole, Cloconazole, Clotrimazole, Econazole, Enilconazole, Fenticonazole, Isoconazole, Ketoconazole, Miconazole, Omoconazole, Oxiconazole, Nitrate, Sulconazole, Tioconazole. Triazoles such as Fluconazole, Itraconazole, Terconazole. Others such as Acrisorcin.Amorolfine, Biphenamine, Bromosalicychloranilide, Buclosamide, Chlophenesin, Ciclopirox, Cloxyquin, Coparaffinate Diamthazole.Dihydrochloπde, Exalamide.Flucytosine, Halethazole, Hexetidine, Loflucarbon, Nifuratel, Potassium Lodide, Propionates, Propionic Acid Pyrithione, Salicylani de.Sulbentine, Tenonitrozole, Tolciclate, - To ndate, Tolnaftate.Tπcetin, Ujothion, Undecylenic Acid ANTIGLAUCOMA such as Dapiprazoke, Dichlorphenamide, Dipivefrin, Pilocarpine ANTIGONADOTROPIN such as Danazol, Gestrinone, Paroxypropione ANTIGOUT such as Colchicine, Probenecid, Sulfinpylrazone Antihistamic Alkylamine Derivatives Such as Acnvastine, Bamipine, Brompheniramine, Chlorpheniramine, Dimethiπdede, Tolpropamine, Tnprolidine Aminoalkyl Ethers such as Bietabautine, Bromodiphenhydramine, Carbinoxamine, Clemastine, Diphenlypyraline, Doxylamine, Embrammine, Medrylamine, Mephenphydramine, p-Methldiphenhydramine, Orphenadnne, Phenyltoloxamine, Pip nhydnnate, Setasine Ethylenediamine Deπvates Such as Alloclamide, p-Bromtπpelennamine, Chloropyramine, Chlorothen, Histapyrrodine, Methafurylene, Methaphenilene, Methapynlene, Phenbenzamine, Pynlamine, Talastine, Thenyldiamine, Thozylamine, Tripelennamine, Zolamine Piperazines such as Certiπzine, Chlorcyclizine, Clocinizine, Hydroxyzine Tncyclies Phenothiazines such as Ahistan, Etymemazine, Fenethazine, N-Hydroxyethy promethazine, Isopromethazine, Mequitaz Inc, Promethazine, Pyrathiazine, Thiazinamium Methyl Sulfate Others such as Azatadine, Clobenzepam, Cyproheptadine, Deptropine, Isothipendyl, Loratadine, Prothipendyl Others Such as Antazohne, Cetoxime, Clemizole, Clobenztropine, Diphenazoline, Diphenhydramine, Mebhydroline, Phenindamine, Terfenadine, Tntoqualine Antihyperlipoproteinemic Aryloxyalkanoic Acid Derivatives such as Bazafibrate, Binifibrate, Ciprofibrate Clinofibrate, Clofibrate Clofibnc Acid Etonfibrate, Fenofibrate Gemfibrozil Nicofibrate Pirifibrate, Ronifibrate, Simfibrate, Theofibrate Bile Acid Sequesterants such as Cholestyramine Resin, Colestipol, Po dexide HMG CoA Reductass Inhibitors such as Lovastatin, Pravastatin, Simvastatin Nicotinic Acid, Derivatives Aluminium Nicotinate, Acipimox, Niceπtol, Nicolonate, Nicomol, Oxiniacic Acid Thyroid Hormones/Analogs such as Etiroxate, thyropropic Acid Others such as Acifran, Azacosterol, Benfluorec, β-Benzalbutyramide, Benzodioxole Camitine, Chondroitin Sulfate, Clomestone, Detaxtran, Dextran Sulfate Sodium 5,8,11 ,14, 17-Eιcosapentaenoιc Acid, Eπtadenine, Famesylated tetrahydro- naphthalenols, Furazbol, Meglutol, Me namide, Mytatπenediol.Naphtyl- tetrahydronaphtyl-diphosphonates, Omithine, γ-Oryzanol, Pentethine, Penataerythπtol Tetraacetate, a-Phenylbutyramide, Phylate Acids And Salts, Pirozadil, Probucol, a- Sisoterol, Sultosihc Acid, Tiadenol, Tπparanol ANTIHYPERTENSIVE Benzothiadiazine Derivatives such as Althιazιde,Bendroflumethιazιde, Benzthiazide, Benzylhydrochlorothiazide, Buthiazide, Chlorothiazide, Chlorthalidone, Cyclopenthiazide, Cyclothiazide, Diazoxide, Epithiazide, Ethiazide, Fenquizone Hydrochlorothiazide, Hydroflumethiazide, Methyclothiazide, Meticrane Metolazone Paraflutizide, Polythiazide, Tetrachlormethiazide Trichlormethiazide N-Carboxyalkyl (peptide/lactam) Derivatives such as Alacepπl, Captopnl, Cilazapπl Enalapπl Enalapnlat, Fosinopnl, Lisinopnl, Moveltipπl, Perindopπl, Quinapnl, Ramipπl Guanidine Derivatives Bethanidine, Debnsoquin, Gyanacline, Guanadrel, Guanazodine, Guancthidine, Guanochlor, Guanoxabenz, Guanoxan Hydrazines/Ohthalazines such as Cadralazine, Dihydralazine, Endralazine Hydracarbazine, Hydralazine, Pheniprazine, Pildralazine, Todralazine Imuidazole Derivatives such as Lofexidine, Phentolamine, Tolonidine Quantemary Ammonium Compounds Azamethonium Chloπsondamine Hexamethonium, Pentacynium, Bιs(methylsulfate), Pentamethonium, Pentolinium Tartate, Phenactopinium, Tπmethidiunum Methosulfate Quinazo ne Derivatives such as Alfuzosin, Bunazosin Reserpine Derivatives such as Bietaserpine, Deserpidine, Rescinnamine Reserpine Syrosingopine Sulfanoamide Derivatives such as Ambuside, Clopamide, Furosemide, Indapamide Quinethazone, Tπpamide, Xipamide Others such as Aimaline, g-Aminobutyπc Acid, Bufeniode, Chlorthalidone, Cicletaine, Ciclosidomine, Cryptenamine Tannates, Flosequinan, Indoramin.Ketanseπn, Metbutamate, Mecamylamine, Methyldopa, Methyl 4-Pyπdyl Ketone Thiosemicarbarzone, Metolazone, Minoxidil Muzo mine, Pargyline Glycine Aminopropargyl Diols, Protoveratnnes, Raubasine, Rescumetol, Saralasin, Sodium Nitroprusside, Ticrynafen, Tnmethaphan, Camsylate, Tryosinase, Urapidil ANTIHYPERTHYROID Such as 2-Amιno-4-methyl-thιazole, 2-Amιnothιazole, Carbimazole, 3,5-Dιbromo-L-tyrosιne, 3,5-Dιιodotyrosιne, Hindeπn, Iodine, lothiouracil, Methimazole, Methylthiouracil, Propylthiouracil, Sodium Perchlorate, Thibenzazoline Thiobarbital, 2-Thιouracιl ANTIHYPOTENSIVE Such as Amezinium Methyl Sulfate, Angiotensin Amide, Etifelmm Etilefnn, Gepefnne ANTIHYPOTHYROID such as Levothyroxine, Liothyronine Thyroid Thryroidin Thyroxine, Tiratπcol ANTI-INFLAMMATORY (NONSTEROIDAL) Aminoarylcarboxy c Acid Derivatives such as Etofenamate, Meclofenamic Acid Mefanamic Acid, Niflumic Acid Arylacetic Acid Derivatives such as Acemetacin, Amfenac, Cinmetacin, Clopirac, Diclofenac, Fenoclofenac, Fenclorac, Fenclozic Acid, Fentiazac, Glucametacin Isoxepac, Lonazolac, Metiazine Acid, Oxametacine Proglumetacin Su ndac Tiaramide, Tolmetin Arylbutyric Acid Derivatives such as Butibufen, Fenbufen Arylcarboxylic Acids such as Clidanac, Ketorolac, Tinoradine Arylpropionic Acid Derivatives such as Bucloxic Acid, Carprofen, Fenoprofen, Flunosaprofen, Ibuprofen, Ibuproxam, Oxaprozin, Piketoprofen, Pirprofen, Praπoprofen, Protizinic Acid, Tiaprofenic Acid Pyrazoles such as Mepinzole Pyrazolones such as Clofezone, Feprazone, Mofebutazone, Oxyphenbutazone, Phenylbutazone, Phenyl Pyrazo dininones, Suxibuzone, Thiazo nobutazone Salicylic Acid Derivatives such as Bromosaligenin, Fendosal, Glycol Salicylate Mesalamine, 1 -Naphthyl Salicylate, Olsalazine, Sulfasalazine Thiazinecarboxamides such as Droxicam, Isoxicam, Piroxicam Others such as e-Acetanidocaproic Acid, S-Adenosylmethionine, 3-Amιno-4- hydroxybutync Acid, Amixetnne, Bendazac, Bucolome, Carbazones Difenpiramide Ditazol, Guaiazulene, Heterocyclic Aminoalkyl Esters of Mycophenolic Acid And Derivatives, Nabumetone, Nimesulide, Orgotein, Oxaceprol, Oxazole Derivatives Paranyline, Pifoxime, 2-subsιtιtuted-4, 6-dι-tertιary-butyl-s-hydroxy-1 ,3-pyromιdιnes, Proquazone, Sialyl Lewis Dimers, Tenidap ANTIMALARIAL such as Acedapsone, Alphaaminoquinolines, 40 Amiπoquinolines, Amodiaquin, Arteether, Artmether, Artemisin, Artesunate, Bebeenne, Chirata, Chlorguanide, Chloroquine, Chloproguanil, Chinchone, Cinchonidine, Cinchonine, Cycloguanil, Euqinine, Gentiopicπn, Halofantnne, Mefloquine Hydrochloride, 3-Methylarsacetιn, Pamaquine, Plasmocid Pπmaquine Pynmethamine, Quinacnne, Quinine, (Acids, Salts And Derivatives), Quinine Formate, Quinine Gluconate, Quinine Tannate, Quinine Urea Hydrochloride, Quinocide, Quinoform, Quino ne, Sodium Arsenate, Diabasic ANTIMIGRAINE such as Akpiropπde, Dihydrergotamine, Ergocornine, Ergocominine Ergocryptine, Ergot, Ergotamine, Flumedroxone Flumedroxone Acetae, Fonazine, Methysergιd(e), Oxetorone, Pizoty ne, Sumatπptan ANTINAUSEANT such as Acetylleucine Monoethanolamine, Bietanautine, Bromopπde Buchzine, Clebopnde, Cyclizine, Dimenhydπnate, Diphenidol, Dompeπdone Gransetron, Mechzine, Methaltjl, Metoclopramide, Metopimazine, Nabilone, Ondansteron, Oxypendyl, Pipamizine, Piprinhydπnate, Scopolamine, Tetrahydrocannabinols, Thiethylperazine, Trimethobenzamide ANTIMEOPLASTIC Alkyl agents Alkyl Sulfonates such as Busylfan, Improsulfan, Piposulfan, Azindines such as Benzodepa, Carboquone, Meturedepa, Uredepa Ethylenimines ans Methylmelamines such as Altertamine, Tπethylenemelamine, Triethylenephosphoramide, Triethylenethiophosphoramide, Trimethylolomelamiπe Nitrogen Mustards such as Chlorambucil, Chlomaphazine, Chclophosphamide, Chclophosphamide, Estramustine, Ifosfamide, Mechlorethamine, Mechlorethamine Oxide Hydrochloride, Melphalan, Novembichin, Phenesteπne, Prednimustine, Trofosfamide, Uracil Mustard Nitrosoureas Carmustine, Chlorozotocin, Fotemustine, Lomustine, Nimustine, Raπimustine Others such as Dacrabazine, Mannomustine, Mitobronitol, Mitolactol, Pipobroman Antibiotics such as Aclacinomycins, Actinomycin F1 , Anthramycin, Azasenne, Bleomycins, Cactinomycin, Carubicin, Carzinophilin, Chromomycins, Dactinomyciπ, Daunorubicin, Carzinophilin, Chromomycins, Dactinomycin, Dauπorubicin, 6-Dιazo-5- oxo-L-naroleucine, Doxorubicin, Epirubicin, Mitomycins, Mycophenolic Acid, Nogalamycin, Olivomycins, Peplomycin, Plicamycin, Profiromycin, Puromycin, Streptonigrin, Streptozocin, Tubercidin, Ubenimex, Zinostatin, Zorubicin Antimetabo tes Folic Acid Analogs such as Deneptenn, Methotrexate, Pteropteπn, Tnmetrexate Purine Analogs Such as Fludarabine, 6-Mercaptopurιne, Thiamipnne, Thiguanaine Pyrimidine Analogs such as Ancitabine, Azacitidine, 6-Azaurιdιne, Carmofur, Cytarabine, Dibexyuπdines, Doxiflundine, Enocitabine, floxuπdine, Fluororacil, Tegafur Enzymes such as L-Asparaginase, Pulmozyme Others such as Aceglatone, Aldophophamide Glycoside, Aminolevulinic Acid, Amsacrine, Bestabucil, Bisantrene, Carnoplarin, Deformide, Demecolcine, Diaziquone, Elfornithine, Elliptimum Acetate, Etoglucid, Etoposide, Gallium Nitrate, Hydroxyurea, Interferon-α, Interferon-β, lnterferon-γ, lnterleukιne-2, Lentinan, Lonidamine, Mitoguazone, Mitoxantrone, Mopidamol, Nitracrine, Pentostatin, Phenamet, Pirarubicin Podophylhnicc Acid, 2-Ethythydrazιde, Procarazine, PSK® , Razoxane, Sizofiran, Spirogermanium, Taxol, Teniposide, Tenuazonic Acid, Tπaziquone, 2,2',2"- Trichlorotnethylamine, Urethan, Vinblastine, Vincnstine, Vindesine ANTINEOPLASTIC(HORMONAL) Androgens such as Calusterone dromistanolone Propionate, Epitiostanol, Mepitiostane, Testolactone Antiadrenals such as Aminoglutethimide, Mitotane, Trilostane Antiandrogens such as Flutamide, Nilutamide Antiestrogens such as Aromatase Inhibiting 4(5)-lmιdazoles ANTINEOPLASTIC ADJUNCT Folic Acid Replenisher such as Fro nic Acid ANTIPARKINSONIAN such as Amantadine, Benserazide, Bictanaunne, Bipeπden Budipine, Carbidopa, Deprenyl, Dexetimide, Diethazine, Droxidopa, Ethopropazine, Ethylbenzhydtamine, Levodopa, Piroheptine, Pndinol, Prodipine, Terguride, Tiapride, Tigloidine ANTIPHEOCHROMOCYTOMA such as Metyrosine, Phenoxybenzamine ANTIPNEUMOCYSTIS such as Efformithine ANTIPROSTATIC HYPERTROPHY such as Proscar® ANTIPROTOSOAL (LEISHMANIA) such as Ethylstinamine, Hydroxystibamidine, N- Methylglucamine, Pentamidine, Stilbamidine ANTIPROTOZOAL (TRICHOMONAS) such as Acearsone, Aminitrozole, Anisomycin, Azanidazole, forminitrazole, furazolidone, Hzanidazole, Lauroguadine, Metronidazole, Nifuratel, Nimorazole, Silver Picrate, Tenonitrozole ANTIPROTOZOAL(TRYPANOSOMA) such as Benznidazole, Eflomithine.L Melarsoprol, Mifutrimox, Oxophenarsine, Puromycin, Quinapyramine, Suiramin Sodium, Trypan Red, Tryparasmide ANTIPRURITIC such as Camphor, Cyproheptadine, Dichlorisone, Glycine, Halmetasone, 3-Hydroxycamphor, Menthol, Mesulphen, Methdilazine, Phenol, Spirit Of Camphor, Trimeprazine ANTIPSORLATIC such as Acitretin, Anthralin, 6-Azaurιdιne, Bergrapten(e) Chrysarobin, Eoretinate, Pyrogallol ANTIPSYCHOTIC Butyrophenones such as Benpendol, Bromperidol, Dropendol, Fluanisone, Haloperidol, Melperone, Moperone, Pipamperone, Sniperone, Timiperone, Trifulpendol Phenothiazines such as Acetophenazine, Bhutaperazine, Carphenazine, Chlorproethiazine, Chlorpromazine, Clospirazine, Mepazine, Mesondazine, Methoxypromazine, Metofenazate, Oxaflumazine, Perazine, Pencyazine, Peπmethazine, Perchloperazine, Promazine, Sulfondazine, Thiopropazate thiondaziane, Trifluoperazine, Triflupromazine Thioxanthenes such as Chlorprothixene, Clopenthixol, Flupentixol, Thiothixene Other such as Alizapnde, Amisulpride, 4-Arylpιperazιnes, 4-Arypιperdιnes, Buramate, Fluspinlene, Moledone, Penfluπdol, Pimozide, Spiπlene, Sulpinde ANTIPYRETIC such as Aconine, Aconite, Aconitine, Phenicarbazide ANTIRICKTTSIAL such as p-Aminobeπzoic Acid ANTISEBORRHEIC such as 3-O-Lauroylpyrιdoxol Diacetate, Piroctone, Resorcinol, Selenium Sulfides, Tioxolone ANTISEPTIC Guanidines Such as Alexidine, Ambazone, Chlorhexidine, Picloxydine Halogens/Halogen Compounds Such as Bronyl Chloride, Calcium lodate, Iodine Monochloπde, Iodine Trichloride, Lodoform, Povidone-lodine, Sodium Hyopchlonte, Sodium lodate, Symclosene, Thymol Iodide, Tnclocarban, Tnclosan, Troclosene Potassium Nitrofumase such as Flrazolidoπe, 2-(Methoxymethyl)-5-Nιtofuran, Nidroxyzone, Nifuroxime, Nifurzide, Nitrofurazone Phenols such as Acetomeroctol, Chloroxylenol, Hexachlorophene, 1 -Napthyl Salicylate, 2,4,6-Trιbromo-m-cresol, 3'4',5-Trιchlorosalιcylanιlιde Quinolines such as Aminoquinuπde, Chloroxine, Chlorquinadol, Cloxyquin, Ethylhydrocupreine, Halquinol, Hydrastine, 8-Hydroxquιnolιne Sulfate Others such as Boric Acid, Chloroazodin, m-Cresyl Acetate, Cuperic Sulfate lchthammol ANTISPASMODIC such as Alibendol, Ambucetamide, Aminopromazine, Bietamiveπne Butavenne, Butropium, Carveπne, Cimetropium, Cinnamedπne, Clebopnde, Connne Hydrobromide, Connne, Difemeπne, Dnsopromine, Dioxaphetyl Butyrate, Drofenine, Ethaveπne, Feclemine, Fenalamide, Fenovenne, Fenpiprane, Flavoxate, Flopropione Gluconic Acid, Guaiactamine, Hydramitrazine, Hymecromone, Leiopyrrole, Mebevenne Moxaveπne.Nafiveπne, Octaveπne, Phenamacide, Phloroglucinol, Pinaveπum, Pipenlate, Pipoxolan, Hydrochloride, Pramiveπn, Propeπdine, Propivane Propyromazine, Prozapine, Racefemine, Rociveπne, Spasmolytol, Stilonium, Tiropramide, Trepibutone, Tncromyl, Tnfolium, Trimebutine, N, N-1 Trιmethyl-3,3- Diphenylpropylamine ANTITHROMOBOTIC such as Anagrelide, Argatroban, Cilostazol Daltroban, Defibrotide, Enoxapaπn, Fraxipaπne®, Indobufen, Lamoparan, Ozagrel Picotamide Plafibnde, Tedelpann, Ticlopidine, Tπflusal ANTITUSSIVE such as Allocamide, Amicibone, Benpropenne, Benzonatate, Bibenzonium, Bromoform, Butamirate, Butethamate, Caramiphen Ethanedisulfonate Carbetapentane, Chlophedianol, Clobutinol, Cloperastine Codeine Methyl Bromide Codeine N-Oxide, Codeine Phosphate, Codeine Sulfate, Cyclexanone, Dextromethorphan, Dibunate Sodium, Dihydrocodeine, Dihydrocodeinone Enol Acetate, Dimemorfan, Dimethoxanate α, α-Dιphenyl-2-pιpeπdιnepropanol, Dropropizine, Drotebanol, Eprazinone, Ethyl Dibunate, Ethylmorphine, Fominoben, Guiaiapate, Hydrocodone, Isoaminile.Levopropoxyphene, Mordofone, Narceine, Normethadonem Noscapine, Oxeladin, Oxolamine, Pholcodine, Picopenne, Pipazethate, Pipeπdione.Prenoxdiazine, Racemethorphan, Tazipnπon, Hydrochloride, Tipepidine, Zipeprol ANTITULCERATIVE such as Aceglutamide Aluminium, Complex, ε-Acctamidocaproic Acid Zinc Salt, Acetoxolone, Arbaprostil, Benexate Hydrochloride, Bismuth Subcitrate Sol(Drιed), Carbenoxolone, Cetraxate, Cimetidine Enprostil, Esaprazole, Famotidine, Ftaxi de, Gefarnate, Guaiazulene, Irsogladine, Nizatidine, Omeprazole, Ornoprostil, Y- Oryzanol, Pifarnine, Pirenzepine, Plaunotol, Ranitidine, Rioprostil, Rosaprostol, Rotraxate,Roxatιdιne Acetate, Sofaicone, Spizofurone, Sucralfate, Teprenone, Tπmoprostil, Thπthiozine, Troxipide, Zohmidine ANTIUROLITHIC such as Acetohydroxamic Acid, Allopurinol, Potassium, Citrate, Succinimide ANTIVENIN such as Lyovac®, Antivenin ANTIVIRAL Puπnes/Pyπmidinones such as 2-Acetyl-Pyrιdιne 5-((2-pyrιdylamιno) thiocarbonyl), Thiocarbonohydrazone, Acyclovir, Dideoxyadenosine, Dideoxycytidine, Dideoxyinosine, Edoxudine, Floxuπdine, Gan clovir, Idoxundine, MADU, Pyπdinon, Tnfluridine, Vidrarbine, Zidovudine Others such as Acetylleucine Monoethanolamine, Acπdianamine, Alkyhsooxazoles Amantadine, Amidinomycin, Cuminaldehyde Thiosemicarbzone, Foscarnet Sodium, Kethoxal, Lysozyme, Methisazone.Moroxydine, Podophyllotoxin, Ribavinn Rimantadine, Stallimycin, Statolon, Thymosins, Tromantadine, Xenazoic Acid ANXIOLYT1C Arylpiperazines such as Buspirone, Gepirone, Ipsapirone, Benzodiazepine, Derivatives Alprazolam, Bromazepam, Camazepam, Chlordiazepoxide, Clobazam, Clorazepate, Chotiazepam, Cloxazolam, Diazepam, Ethyl Loflazepate, Etizolam, Fluidazepam, Flutazolam, Flutoprazepam, Halazepam, Ketazolam, Lorazepam, Loxapine, Medazepam, Metaclazepam, Mexazolam Nordazepam, Oxazepam, Oxazolam, Pinazepam.Prazepam, Tofisopam Carbamates such as Cyclabarmate, Emylcamate, Hydroxyphenamate, Meprobamate, Phenoprobamate, Tybamate Others Alpidem, Benzoctamine, Captodiamine, Chlormezanone, Etifoxine, Fluoresone, Glutamic Acid, Hydroxyzine, Mecloralurea, Mephenoxalone, Oxanamide, Phenaglycodol, Su clone BENZODIAZEPINE ANTAGONIST such as Flumazenil BRONCHODILATOR Ephednne, Derivatives such as Albuterol, Bambuterol, Bitolterol, Carbuterol, Clenbuterol, Clorprena ne, Dioxethedπne, Eprozmol, Etafednne, Ethylnorepinephnne, Fenoterol, Hexoprenaline, Isoethanne, Isoproterenol, Mabuterol, Metaproterenol, N- Methylephedrine, Pirbuterol, Procaterol, Protokylol, Reproterol, Rimiterol, Soterenol, Terbutahne, Tulobuterol Quaternary Ammonium Compounds such as Clutropium Bromide, Oxitropium Bromide Xanthine Derivatives such as Acefylline, Acefylline Ambuphylline, Aminophylline, Bamifylline, Choline Theophyllinate, Doxofylline, Dyphylline, Enprofylline, Etamiphylline, Etofylline, Guaithyllme, Proxyphylline, Theobromine, 1 -Theobromιneaceatιc Acid, Theophylline Others such as Methoxyphenanime, Tretoquinol CALCIUM CHANNEL BLOCKER Arylalkylamines such as Bepndil, Ditiazem, Fendiline, Gallopamil, Terodi ne, Verapamil Dihydropyridine denvates such as Felodipine, Isradipine Nicardipine Nifedipine Nilvadipine, Nimodipine, Nisoldine, Nitrendipine Piperazine Derivatives Such as Flunaπsine Others Such as Perhexiline CALCIUM REGULATOR such as Calcifediol, Calcitonin, Calcitnol, Clodronic Acid, Dihydrotachysterol, Elctonin, Etidronic Acid, Ipnflavone, Pamidronic Acid, Parathyroid Hormone Tenparatide Acetate CARDIOTONIC such as Acetyldigititoxins, 2-Amιno 4-Pιcoiιne, Amπnone, Buclasdesine, Cerberoside, Camphotamide, Convallatoxin, Cymarin, Denopamine, Deslanoside, Ditalin, Digitalis, Digitoxin, Digoxin, Dobutamine, Dopamine, Dopexamine, Enoximone, Erythrophleine, Fenalcomine, Gitahn, Gitoxin, Glycocyamine, Heptaminol, Hydrastinine, Lanotodises, Metamivam, Substituted Methoxyphenyl-4, 5-dιhydro-3(2H)-pπdazιnones, Milπonone, Nernfolin, Oleandxin, Ouabain, Oxyfedπne, Prenalterol, Proscillandin, Resibufogenin, Scillaren, Scillarenin, Strophanthin, Sulmazole, Theobromine, Xamoterol CHELATING AGENT such as Deferozmine, Edetate Calcium Disodium, Edetate Disodium, Edeate Sodium, Edetate Tnsodium, Pentetate Calcium Trisodium, Pentectic Acid, Succimer, Tnentine CHOLECYSTOKINN ANTAGONIST (CCK Antagonist) CHOLELITHOLYTIC AGENT such as Chenodiol, Methyl tert-Butyl Ether, Monooctanoin, Ursodiol CHOLERETIC such as Alibendol, Anethole Tnthion, Azintamide, Cholic Acid, Cicrotoic Acid, Clanobutin, Cyclobutyrol, Cyclovalone, Cynarιn(e) Dehydrochohc Acid, Deoxycholic Acid, Dimecrotic Acid, d-Ethylbenzyl Alcohol, Exιproben,Feguprol, Fencibutirol, Fenipentol, Florantyrone, Hymecromone, Menbutone, 3- (0- Methoxyphenyl)-2-Phenylacrylιc Acid, Metochalcone, Moquizone, Osalmid, Ox Bile Extract, 4,4'-Oxydι-2-Butanol, Piprozolin, Prozapine, 4-Salιcyloymorpholιne, Sincahde, Taurochohc Acid, Timonacic, Tocamphyl, Trepibutone, Vanitiohde CHOLINERGIC such as Acec dine, Acetylcho ne, Acetylcho de, Aclatonium, Napadisilate, Benzpynnium, Bromide, Bethanechol, Carbachol, Carpronium, Demecaπum, Dexpanthenol, Dnsopropyl Paraoxon, Echothiophate, Edrophomium, Esendine, Furtrethonium, Isoflurophate, Methachohne, Chloride, Muscanne Neostigmine, Oxapropanium, Physostigmine, Pyπdostigmine CHOLINESTERASE INHIBITOR such as Ambenonium, Distigmine, Galanthamine CHOLINESTERASE REACTIVATOR such as Obidoximine, Pralidoxime CNS STIMULANT/AGENT such as Amineptine, Amphetimine, Amphetamiml, Bemegπde, Benzphetamine, Brucine, Caffeine, Chlorphentermine, Cloferciclan, Cloratermine, Coca, Demanyl Phosphate, Dexoxadrol, Dextroamphetamine Sulfate, Diethlpropion, N- Ethylamphetamine, Ethamivan, Fencamfamine, Fenethylline, Fenosolone, Flurothyl, Hexacyclonate Sodium, homocamfin, Mazindol, Megexamide, Methamphetamine, Methylphenidate, Nicotine, Nicorinic Agonist, Nikethamide, Pemo ne, Penthylenetrazole, Phenidimetrazine, Phenmetrazine, Phentermine, Picrotoxin, Pipradrol, Pro ntane, Pyrovalerone, Terahydrobenzothienpphyndines DECONGESTANT such as Cafaminol, nordefnn DENTAL CATTIES PROPHYLACTIC such as sodium fluoride DEPIGMENTOR such as Hydroquinine, Hydroquinone, Monobenzone DIURETIC Organomercurials such as Chlormerodnn, Meralluπde, Mercamphamide Mercaptomeπn Sodium, Mercumallyic Acid, Mercumatillin Sodium, Mercurous Chloride Mersalyl Ptendines such as Furterence, Triameterene Puπnes such as 7-Morpholιnomethyltheophyllιne, Pamabrom, Protheobromine Theobromide Steroids such as Canrenone, Oleandπn, Spironolactone Sulfonamide Derivatives such as Acetazolmide, Azosemidem, Bumetanide Butazolamide, Chloraminophenamide, Clofenamide, Clorexolene, Dιphenylmethane-4 4'-Dιsulfonamιde, Disulfamide, Ethoxzolamide, Flumethiazide, Mefruside, Methazolamide, Piretanide Torasemide Uracils such as Aminometradine, Amisometradine Others such as Amanozmde, Amiloride, Arbutin, Chlorazanil, Ethacrynic Acid, Etozolin, Isosorbide, Mannitol, Methochalone, Pethexilline, Urea DOPAMINE RECEPTOR AGONIST such as Bromocπptine, Fenoldopam, Lisunde, Naxagohde, Pergohde ECTOPARASITICIDE such as Amitraz, Brenzyl Benzoate, Carbaryl, Crotamiron, DDT Dixanthogen, Isobornyl Thiocyanoacetate (Technical), Lime Sulfurated Solution Lindane, Malathion, Mercuric Oleate, Sulphur (Pharmaceutical) ENZYME Digestive such as a - Amylase(Swιne Pancreas), Lipase, Pancrelipase, Pepsin, Rennim Penicillin Inactivating such as Penicillinase Proteolytic such as Colagenase, Chymopapain, Chymotrypsins, Papain, Trypsin ENZYME INDUCER (HEPATIC) such as Flumecinol ESTROGEN Nonsteroidal such as Benzestrol, Broparoestrol, Chlorotπanisene, Dienestrol, Diethyistilbestrol Diethyistilbestrol Dipropπonate, Dimestrol Fosfestrol, Hexestrol, Methallenstπl Methestrol Steroidal such as Colpormon, Conugated Estrogenic Hormones, Equilenin, Equilin, Estenfied Estrogens Esteropipate, 17b-Estradιol, Estradiol, estradiol Benzoate, Estradiol 17b-Cypιonate, Estrone, Ethibyl Estradiol, Mestranol, Moxestrol, Mytat enediol, Poiyestradiol Phosphate, Qumestradiol, Quinestrol GASTRIC SECRECTION INHIBITOR such as Enterogastrone, Octreotide GLUCOCORTICOID such as 21-Acetoxyprefnenolone, Aalclometasone, Algestone Amicinonide, Beclomethasone, Betamethasone, Betamethasone, Dipropionate, Budesonide, Chloroprednisone, Clobetasol, Blovestasone, Clocortolone, Cloprednol , Corticosterone, Cortisone, Cortisone, Cortivazol, Deflazacort, Desonide, Desoximetasone, Dexamethasone, Diflorasone, Diflucortolone, Difluprednate Enoxolone, Fluazacort, Flucloronide, Flumehtasone, Flunisolide, Fluocinolone, Acetonide, Fluocinonide, Fluocortin, Butyl, Fluocortolone, Fluorometholone, Fluperolone, Acetate, Fluprednidene, Acetate, Fluprednisolone, Flurandrenohde, Formocortal, Halcinonide, Halometasone, Halopredone Acetate, Hydrocotramate, Hydrocortisone, Hydrocortisone Acetate, Hydrocortisone, Phosphate, Hydrocortisone 21 -Sodium Succinate, Hydrocortisone Tebutate, Mazipredone, Medrysone, Meprednisone, Methyolprednisolone, Mometasone, Furcate, Paramethasone, Prednicarbate, Prednisolone, Prednisolone 21 -Dιethylamιnoacerate, Prednisone Sodium Succinate, Prednisolone Sodium Phosphate, Prednisolone Sodium 21 -m- Sulfobenzoate, Prednisolone 21-Stearoylglycolate, Prednisolone Tebutatem Orednisolone 21-Tπmethylacatate, Prednisone, Prednival.Prednylidene, Prednylident 21 -Dιethlamιnoacatate, Tixocoratal, Triamcinolone, Triamcinolone, Acetonide, Triamcinolone, Benetonide, Tnamcinolone, Hexacetonide, GONADSTIMULATING PRINCIPLE such as Clomiphene, Cyclofenil, Epimestrol FSH, HCG, LH-RH GONADOTROPIC HORMONE such as LH, PMSG GROWTH HORMONE INHIBITOR such as Somatostatin GROWTH HORMONE RELEASING FACTOR such as Semorelin GROWTH STIMULANT such as Somatotropin HEMOLYTIC such as Phenylhydrazine HEPARIN ANTAGONIST such as Hexadimethnne Protamines HEAPATOPROTECTANT such as Betaine, Cltolone, Malotilate, Orazamide Phosphorylcholiπe, Protoporphynn IX, Silymaπn-Group, Thiotic Acid, IMMUNOMODULATOR such as Amiprilose, Bucillamine, Ditiocarb Sodium, Iπosine Pranobex, Muroctasin, Platonin, Procodazole, Tetramisole, 6-Ary 1 -5-6- Dιgydroιmιdazol-(2,1 -B) Thιazole Derivatives, Thymomodulin, Thymopentin IMMUNOSUPPRESSANT such as Cyclophi n, Cyclosponns, FK-506, Mizonbine, Rapamycin, Rapamycin Sulfamates IONEXCHANGE RESIN such as Caracry c Resins, Resodec, Sodium Polystyren Sulfonate LACTATION STIMULATING HORMONE such as Prolactin LH-RH AGONIST such as Buserelin, Goserehn, Leupro de, Nafarelin, Tnptorelin LIPOTROPIC such as N-Acetylmethionine, Choline Chloride, Choline Dehydrocholate, Choline Dihydrogen Citrate, Insitol, Lecithin, Methionine LUPUS ERYTHEMATOSUS SUPPRESSANT such as Bismuth Sodium Triglycollamate, Bismuth Subsahcylate MINERALOCORTICOID such as Aldosterone, Deoxycorticosterone, Fludrocortisone MIOTIC such as Pilocarpus MONOAMINE OXIDASE INHIBITOR such as Phenoxypropazine, Pivyalybenzhydrazine MUCOLYTIC such as Acetylcysteine, Bromhexine, Carbocysteine, Domiodol, Letosteine, Mecysteine, Mesna, Sobrerol, Stepronin, Tiopronin, Tyloxapol MUSCLE RELAXANT (SKELETAL) such as Alfoqualone Alcuronium, Atracunum Besylate, Baclofen, Benzoquinonium, C-Calebassine, Cansoprodol, Chlorphenesin Carbamte, Chlozoxazone, Curare, Cyclobenzapnne, Dantrolene, Decamethonium, Epensone, Fazadinium, Flumetramide, Gallamine, Tπethiodide, Hexacarbacho ne, Hexafluorenium, Idrocilamide, Lauexium Methyl Sulfate, Leptodactyline, Memantine, Mephenesin, Metaxalone, Methocarbamol, Metocunne Iodide, Pancuronium, Pipecuriym, Promoxilane, Quinine Sulfate, Styramate, Succiπylcholine, Succinylcholiπe Suxethonium Bromide, Tetrazepam, Thiocolchicoside, Tizanidine, Tolpensone Tubocuranne, Vecuronium, Zoxolamien NARCOTIC ANTAGONIST such as Amiphenazole, Cyclazocine, Levallorphan, Nadide, Nalmagene, Nalorphine, Nalorphine Dinicotinate, Naloxone, Naltrexone NEUROPROTECTIVE such as Dizocilpine NOOTROPIC such as Aceglutamide, Acetylcarnitine, Aniracetam, Bifematlane, Exifone Fipexide, Idebenone, Indeloxazune, Nizofenone, Oxiracetam, Piracetam, Propentofylline, Propentofylhne Pyπtinol OPHTHALMIC AGENT such as 15-Ketoprostaglandιns OVARIAN HORMONE such as Relaxin OXYTOCIC such as Carboprost, Cargutocin, Deaminoxytocin, Erogonovine, Gemeprost, Methylergonovine, Oxytocin, Pituitary (Posterior), Prostaglandin E2, Prostaglandin F2a, Sparteine PEPSIN INIBITOR such as Sodium Amylosulfate PERISTALTIC STIMULANT such as Cisapnde PROGESTOGEN such as Allylestrenol Anagestone, Chlormadinone Acetate, Delmadiπone Acetate, Dmegestone, Desogestrel, Dimethisterone, Dydrogesterone, Ethinylestrenol, Ethisterone, Ethynodiol, Ethynodiol Diacetate, Flurogestone Acetate, Gestodene, Gestonorone Caproate, Haloprogesterone, 17-Hydroxy-16-Methylene- Progesterone, 17-Hydroxyprogesterone, 17a-Hydroxygesterone Caproate, Lynestenol, Medtogestone, Medroxyprogesterone, Megestrol, Acetate, Melengestrol, Norethindrone, Norethindrone Acetate, Norethynodrel, Norgesterone, Norgestimate, Norgestrel, Norgestrienone, 19-Norprogesterone,Norvιnιsterone, Pentagestrone, Progesterone, Promegestone, Quingestrone, Trengestone PROLACTIN INHIBITOR such as Metago ne PROSTAGLANDIN/PROSTAGLANDIN ANALOG such as Bmeprost, Prostacychn, Prostaglandin E1 ,Sulprostone PROTEASE INHIBITOR such as Aprotinin, Camostat, Ganexate, Nagamostat RESPIRATORY STIMULANT such as Almitnne, Dimefine, Dimorpholamine, Doxapram, Lobeline, Mepixanox, Pimecione, Sodium, Succinate, Tacrine SCLEROSING AGENT such as Ethanolamine, Ethylamine, 2-Hexyldecanoιc Acid, Sodium Ricinoleate, Sodium Tetradecyl Sulgate, Tnbenoside SEDATIVE/HYPNOTIC Acyclic Ureides such as Acecarnromal, Apronalide, Bomisovalum, Capunde, Carbromal, Ectylurea Alcohols such as Chlorhexadol, Ethchlorvynol 4-Methyl-5- thiazolecthanol, Tert-Pentyl Alcohol, 2,2,2,-Trιchloroethanol Amides such as Butoctamide, Diethylboromoacetamide, Ibrotamide, Isovaleryl Diethylamide, Niaprazine, Tncetamide, Tnmerozine, Zodlpidem, Zopiclone, Barbituric Acid Derivatives Such as Allobarbital, Amobarbital, Aprobarbital, Barbital, Brailabarbital, Butabarbital, Sodium, Butalbital, Burallylonal, Butethal.Carbubarb Cyclobarbital Cyclopentobarbital, Enallylpropymal, 5-Ethyl-5-(Pιperιdyl) Barbituric Acid, 5-Furϊuryl-5- Isopropylbarbitunc Acid, Heptabarbital, Hexethal, Sodium, Hexobarbital, Mephobarbital Methitural, Narocobarbital, Nealbarbital, Pmtobarbital Sodium, Phenallymal Phenobarbital, Phenobarbital Sodium, Phenylmethylbarbituric Acid, Probarbital, Propallylonal, Proxibarbal, Reposal, Secobarbital Sodium, Talbutal, Tetrabarbital, Vinbarbital Sodium, Vinylbiral Benzodiazopine Derivatives such as Brotizolam, Doxefazopam, Estazolam, Flunitrazopam, Flurazopam, Haloxdazolam, Loprazolam, Lormetazepam, Nitrazepam Quazepam, Temasepam, Triazolam Bromides such as Ammonium Bromide, Calcium Bromide, Calcium Bromilactobioπate, Lithium Bromide, Magnesium Bromide, Potassium Bromide, Sodium Bromide Carbamates such as Amyl Carbamate(Tertιary), Ethinamide, Hexaprpymate Meparfynol, Carbamate, Novonal, Tncholorourethan Chloral Derivatives such as Carbocloral, Chloral Betaine, Chloral Formamide, Chlotal Hydrate, Chloralantipynne, Dichloralphenazone, Pentaerythritol Chloral, Tnclofos Pipendinediones such as Glutehimide, Methyprylon, Pipenone, Pynthyldione Taglutimide, Tha domide Quinazolone Derivatives such as Etaqualone, Mecloqualone, Methaqualone Others Such as Acetal, Acetophenone, Aldol, Ammonium Valerate, Amphenidone, d-Bomyl a- Bromoisovalerate, d-Bomyl Isovaletate, Bromoform, Calcium 2-Ethylbutanoate, Carfinate, a-Chlorolose, Clomethiazole, Cycpπpedium Doxylamine, Etodroxizine Etomidate, Feradiazole, Homofenazine, Hydrobromic Acid, Mecloxamine, Menthyl Valerate, Opium, Paraldehyde, Perlapine, Propiomazine, Rilmazafone, Sodium Oxybate, Sulfoπethylmethane, Sulfonmethane THROMBOLYTIC such as APSAC, Plasmin, Pro-Urokinase, Streptokinass, Tissue Plasminogen Activator, Urokinass THYROTROPIC HORMONE such as TRH.TSH MISCELLANEOUS- Vitamins, Minerals as well as other Nutrients, Vit B1 ,B2,B6,B12 and other water soluble vitamins, Vitamin C, Vitamin A,D,E And Other Oil Soluble Vitamins, Iron, Zinc and Other Micronutrients and their combinations with Vitamins, Antioxidants i e Betacarotene and combination thereof with Vitamins, Gensing and other rejuvenants and suitable combinations of drugs disclosed above The suitable mucoadhesive agents include cellulose derivatives like methyl cellulose, hydroxypropylmethyl cellulose, hydroxypropyl cellulose, cellulose acetate phthalate cellulose acetate, cellulose acetate butyrate, cellulose acetate propionate cellulose acetate tπmellitae, cellulose carboxymethyl ethers and their salts, hydroxypropymethyl cellulose phthalate, hydroxypropylmethyl cellulose acetate succinate, polyethylene, polyvinyl acetate (homopolymer), polyvinyl acetate phthalate, propylene glycolalginate PVM//MA copolymer, PVP/dimethiconylacrylate/ polycarbamyl/polyglycolester, PVP/dimethylaminoethylmethacrylate/ polycarbamyl polyglycol ester PVP/ polycarbamyl polyglycol ester, PVP/VA copolymer, gelatin and Gelatin derivatives Alginates, Carbomers, Polycarbophils Methacr ylic acid copolymers Carrageenans, pectins, chitosans, cyclodextπns, lecithins Natural gums containing galactomannans like xanthan gum, Acacia, tragacanth agar, guar gum and the like The fast soluble part of the sweetener gives a rapid burst of the sweetness whereas the mucoadhesive form binds to the oral mucosa and gives a prolonged sweet taste thereby effectively masking the bitter or bad after-taste of the pharmaceutically active agents The conventional therapeutically acceptable additives like binding agents, Lubricants, Disintegrants, Flavouring agents, colouring agents, pH modifiers and Wetting agents may be added to the pharmaceutical composition prepared If desired, the active pharmaceutical agent may be first subjected to the conventional taste neutralization treatment like forming matrix microspheres, microencapsulation, complexation and the like The compressed tablets have sufficient mechanical strength which allows them to be packed in normal push-through type blister packages and does not require special packaging like peel-off blisters The present invention is further exemplified by the following examples Example 1 Step 1 : Preparation of non-sugar sweetener in mucoadhesive form Aspartame 20 OOg PVM/MA Copolymer(Gantrez AN 169) 0 40g Acetone 20 00ml Dissolve Gantrez AN 169 in 20 ml Acetone Granulate Aspartame with this solution and dry at 40°C Sift through 60 mesh sieve Step 2. Tablet formulation Nιmesulιde(Drug/Pharmacetιcal agent) 100 Omg Mannitol 204 5mg Aspartame of step 1 in mucoadhesive form 7 Omg . , 1 omg Sodium Starch Glycolate 3 Omg Magnesium Stearate 4 Omg Sift all the ingredients through 40 mesh sieve and blend Compress into tablets at a hardness of 1 to 5 kg Example 2 Step 1. Preparation of non-sugar Sweetener in Mucoadhesive form: Aspartame 20 OOg Carbomer( carbopol 934P) 0 40g Water 20 00ml Disperse Carbopol 934P in 20ml Water Granulate Aspartame with it and dry at 40°C Sift through 60 mesh sieve Step 2: Tablet formulation Nιmesulιde(Drug/Pharmaceutιcal agent) 100 Omg Mannitol 204 5mg Aspartame 3 Omg Aspartame of step 1 in mucoadhesive form 4 Omg Flavour 1 5mg Sodium starch glycolate 3 Omg Magnesium Stearate 4 Omg Sift all the ingredients through 40 mesh sieve and blend Compress into tablets at a hardness of 1 to 5kg Example 3: Step: 1 Taste neutralization of drug substance. Ibuprofen (Drug/Pharmaceutical agent) 95 95g Tnbehenin 4 OOg Polysorbate 80 0 05g Water 40 00ml Heat water to about 50°C-60°C Add polysorbate 80 and mix Under stirring add Tnbehenin followed by Ibuprofen A wet dough will be formed Cool it to 35°C Size it through 20 mesh sieve Dry at about 45°C till moisture content is 1 to 3% Sift through 60 mesh sieve Step 2: Tablet Formulation Ibuprofen from step 1 ~ ~" 200 Omg Equivalent to Ibuprofen >- Xyhto _ 204 5mg Aspartame in mucoadhesive form 7 00mg (from step 1 of example 2) Flavour 1 5mg Sodium Starch Glycolate 3 Omg Magnesium Stearate 4 Omg Sift all the ingredients through 40 mesh sieve and blend Compress into tablets at a hardness of 1 to 5kg Example 4 %w/w Cιsapπde(Drug/Pharmaceutιcal agent) 2 50 Liquid 0 25 Sorbitol 84 75 Sodium Starch Glycollate 5 00 Croscarmellose Sodium 1 25 Magnesium Stearate 1 25 Aspartame in mucoadhesive form 3 00 (from step 1 of example 1 ) Colloidal Silicon Dioxide 1 25 Flavour 0 75 Pass the drug through mesh no 60(BSS) sieve Granulate the drug with a solution of Liquid Paraffin in Dichloromethane and pass through mesh no 40(BSS) sieve Dry at a temperature of 45-50°C Sift Sorbitol through mesh no 60(BSS) sieve and mix with drug containing Liquid Paraffin This blend is then granulated with water and then dried at a temperature of 50°-60°C The dried granules are sifted through mesh no 22(BSS) sieve Sift Sodium Starch Glycollate, Magnesium, Stearate, Colloidal Silicon Dioxide, Crosscarmellose Sodium, Aspartame (in mucoadhesive form) and Flavours through mesh No.30(BSS) sieve and mix the above said bulk. Compress into tablets using conventional tabletting machine at a hardness of 1-3 kg. Example 6 %w w CetirizineDihydrochloride 2.5 (Drug/Pharmaceutical agent) Crosslinked Polyacrylic Acid(lon -exchange 10.0 resin) Hydrochloric Acid q.s.to adjust pH Mannitol 64.5 Croscarmellose Sodium 3.75 Povidone 0.25 Aspartame in mucoadhesive form 6.25 (from step 1 of example 1) Magnesium Stearate 0.50 Aerosil 0.75 Sodium Starch Glycollate 3.75 Sodium Chloride 3.00 Citric Acid 2.00 Flavour 2.75 Dissolve Cetirizine dihydroxhloride in 20 times of its weight of water. Add Crosslinked Polyacrylic Acid in small increments with constant stirring. Adjust pH to 3 with hydrochloric acid. Keep aside for 1 to 6 hours and then decant the water. Wash the sediment with water atleast twice. Dry the sediment at 40 to 50°c. Pass through sieve of mesh no 60 (BSS). Mix with pre-sifted (through mesh no.30BBS) blend of Mannitol, Croscarmellose Sodium, Povidone, Aspartame (in mucoadhesive form), Magnesium Stearate, Aerosil, Sodium Starch Glycollate, Sodium Chloride, Citric Acid and Flavour. Compress into tablets using conventional tabletting machine at a hardness of 1-3kg. Example 6 Step 1. Preparation of non-sugar in Mucoadhesive form:- Sacchaπn Sodium 100 OOg Polycarbophil (Noveon AA-1 ) 4 OOg Water 10 OOg Disperse Polycarbophil in Water Granulate Saccharin Sodium with this dispersion Dry at 50°C and sift through mesh no 40(BSS) Step 2 %w/w Chloroquine Phosphate (Drug/Pharmaceutical agent) 10 0 Crosslinked Polyacrylic Acid, Potassium salt 20 0 (Ion-exchange resin) Hydrochloric Acid q s to adjust pH Mannitol 51 50 Croscarmellose Sodium 0 25 Povidone 6 25 Aspartame in mucoadhesive form (from step 1 of example 1 ) Magnesium Stearate 0 50 Sodium Starch Glycollate 3 75 Sodium Chloride 3 00 Citric Acid 2 00 Flavour 2 75 Dissolve Chloroquine Phosphate in 20 times of its weight of water Add Crosslinked Polyacrylic Acid in small increments with constant stirring Adjust pH to 6 with hydrochloric acid Keep aside for 1 to 6 hours and hen decant the water Wash the sediment with water atleast twice Dry the sediment at 40° to 50°C Pass through sieve of mesh no 60 (BSS) Mix with pre-sifted (through mesh no 30 BSS) blend of Mannitol, Povidone, Saccharin Sodium ( in mucoadhesive form), magnesium Stearate, Sodium Starch Glycollate, Sodium Chloride, Citric Acid and Flavour Compress into tablets using conventional tabletting machine at a hardness of 1-3kg Example 7 Step 1 : Taste neutralization of drug substance. Ascorbic Acid 96 OOg Gelatin 4 OOg Water 30 OOml Heat water to about 60°C - 70°C Add Gelatin and dissolve Coat the Ascorbic Acid by sprayaing the gelatin solution using fluidized bed coater Size the coated drug powder through 40 mesh sieve Step 2: Mucoadhesive Sweetener Ammonium Glycirrhizinate 20 OOg PVM/MA Copolymer 0 40g (gantrez AN 169) Acetone 20 OOml Dissolve Gantrez AN 169 in 20 ml Acetone, Granulate Ammonium Glycirrhizinate with this solution and dry at 40°C Sift through 60 mesh sieve Step 3: Tablet Formulation Ascorbic Acid from step 1 Equivalent to Ascorbic Acid 100 Omg Sorbitol 204 5mg Ammonium Glycirrhizinate in Mucoadhesive form 7 OOmg (from step 2) Flavour 1 5mg Sodium Starch Glycolate 3 Omg Magnesium Stearate 4 Omg Λ t 41 Sift all the ingredients through 40 mesh sieve and blend Compress into tablets at a hardness of 1 to 5 kg Example 8 :Tablet Formulation Interferon (Alpha)equιvalent to 18 Million I U Mannitol 204 5mg Aspartame in mucoadhesive form 7 Omg (from step 1 of example 1 ) Flavour 1 5mg Sodium Starch Glycolate 3 Omg Magnesium Stearate 4 Omg Sift all the ingredients through 40 mesh sieve and blend Compress into tablets at a hardness of 1 to 3 kg Example 9 Alprazolam 1 mg Isomalt 98 9mg Aspartame 0 03mg Acesulfam 0 03mg Neohespendine DC in 0 04mg Mucoadhesive form Sift all the ingredients through 30 mesh sieve and blend Compress into tablets at a hardness of 1 to 3 kg The advantages of the present invention are a) The pharmaceutical tablets prepared according to the present invention dissolve/disperse in the mouth within one minute requiring very little amount of body fluids like saliva to produce a solution or suspension of the drug for oral administration b) The tablet leaves a prolonged sweet taste in the mouth c) The un-pleasant or bitter taste of the drug is masked without significantly interfering the dissolution and ultimate bioavailability of the drug present of the tablet d) The process of this invention has low manufacturing cost avoiding the special and costly techniques like Lyophilization, Spray-drying and the like Since many apparently different embodiments of the present invention could be made without departing from the spirit and scope thereof, it is intended that the description of the invention herein be interpreted as being illustrative only and not limiting in any manner whatsoever

Claims: Claim - A novel fast dissolving pharmaceutical composition in solid dosage form with prolonged sweet taste which comprises a) At least one pharmaceutical active agent such as herein described in an amount of from 0 1 to 99 weιght% b) At least one water soluble sugar, such as herein described, in an amount of from 5 to 95 weight % of the total dosage form c) At least one non-sugar sweetner, such as herein described, in their normal fast release form in an amount of from 0 to 10 weight % of the total dosage form d) At least one non-sugar sweetner, such as herein described, in a mucoadhesive slow release form obtained as herein described in an amount of from 0 5 to 20 weight % of the total dosage form A composition as claimed in claim 1 wherein the water soluble sugar is Mannitol, Sorbitol and /or Xy tol A composition as claimed in claim 2 wherein the non-sugar sweetner is Isomalt Aspartame, Acesulfame potassium, Saccharine Sodium, Cyclamates Neohespevidine and/ or Glycirrhizin A process for the preparation of a fast dissolving pharmaceutical composition in solid dosage form with prolonged sweet taste which comprises mixing the following ingredients - a) At least one drug/pharmaceutically active agent such as herein described in an amount of from 0 1 to 99 weight % b) Atleast one water soluble sugar, such as herein described in an amount of from 5 to 99 weight % of the total dosage form c) Atleast one non-sugar sweetner, such as herein described, in their normal fast release form in an amount of from 0 to 99 weight % of the total dosage form d) Atleast one non-sugar sweetner, such as herein described in a mucoadhesive slow release form obtained as herein described in an amount of from 0 005 to 20 weight % of the total dosage form and compressing the resulting mixture obtained or any other solid dosage form 5 A process as claimed in claim 4 wherein the water soluble sugar is Mannitol, Sorbitol and /or Xylitol 6 A process as claimed in claim 4 and 5 wherein the non-sugar sweetner is Isomalt Aspartame, Acesulfame potassium, Saccharine sodium, Cyclamates Neohespendine and / or Glycirrhizin 7 A process as claimed in claims 4 to 6 wherein conventional thereapeutically acceptable additives like Binding agents, Lubricants, Disintegrants, Flavouring agents, Colouring agents, pH modifiers, and Wetting agent may be added to the pharmaceutical composition 8 A novel fast dissolving pharmaceutical composition in solid dosage form with prolonged sweet taste substantially as herein described with reference to the foregoing description and the accompanying examples 9 A process for the preparation of a novel fast dissolving pharmaceutical composition in solid dosage form with prolonged sweet taste substantially as herein described with reference to the foregoing description and the accompanying examples

Inventors: JAIN RAJESH, SINGH AMARJIT, JAIN, RAJESH, SINGH, AMARJIT
Applicants: JAIN RAJESH, PANACEA BIOTEC LTD, SINGH AMARJIT, JAIN, RAJESH, PANACEA BIOTEC LIMITED, SINGH, AMARJIT
Application year: 2000
Main classification: A61K9
IPC codes: A61K9