Title of Invention | "FAST DISSOLVING PHARMACEUTICAL COMPOSITIONS IN SOLID FORM WITH PROLONGED SWEET TASTE AND A PROCESS FOR THE MANUFACTURE THEREOF " |
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Abstract | A novel fast dissolving pharmaceutical composition in solid dosage form with a prolonged sweet taste is provided which comprises at least one pharmaceutical active agent in an amount of from 0.1 to 99 weight % of the total dosage form; at least one water soluble sugar in an amount of from 5 to 95 weight % of the total dosage form; at least one non-sugar sweetener in a fast release form in an amount of from greater than 0 to 10 weight % of the total dosage form; and at least one non-sugar sweetener in a mucoadhesive slow release form in an amount of from 0.5 to 20 weight % of the total dosage form. Also provided is the process of manufacture of such novel compositions. |
Full Text | 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 form like tablets and capsules should be modified 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 freeze-drying 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 manufacturing by using partially hygroscopic shearform matrices. Such matrices are prepared from sugar carriers using a flash-heat process. Further U.S. Patent No. 5,112,616 discloses the use of solid selected from polyethylene glycols and glycerides, wherein glycerides 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 amino 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 a prolonged sweet taste which comprises: a) At least one pharmaceutical 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 sweetener, such as herein described, in their normal fast release form in an amount of from 0 to 10 weight % of the total dosage form; and d) At least one non-sugar sweetener, 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 is 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 % b) At least one water soluble sugar, such as herein described, in an amount of form 5 to 95 weight % of the total dosage form; c) At least one non-sugar sweetener, such as herein described, in their normal fast release form in an amount of from 0 to 10 weight % of the total dosage form; and d) At least one non-sugar sweetener, 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 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 Mannitol, Sorbitol, Xylitol and the like. The non-sugar sweeteners 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 sweetener in a mucoadhesive slow release form is obtained by mixing, coating, granulating, encapsulation, matrix formulation or complexation of a non-sugar sweetener 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- a- ADRENERGIC AGONIST such as Adrafinil, Adrenolone, Amidephrine, Apraclonidine, Budralazine, Clonidine, Cyclopentamine, Detomidine, Dimetofrine, Dipivefrin, Ephedrine, Epinephrine, Fenoxazoline.Guanbenz, Guanafacine, Hydroxyamphetamine, Ibopamine, Indanazoline, Isomethepten, Mephentermine, Metaraminol, Methoxamine, Methylhexaneamine, Metizolene, Midodrine, Naphazoline, Norepinephrine, Norfenefrine, Octodrine, Octopamine, Oxymetazoline, Phenylephrine, Phenylpropanolamine, Phenylpropymethylamine, Pholedrine, Propylhexedrine, Pseudoephredrine, Rilmenedine, Synephrine, Tetrahydrozoline, Tiamenidine, Tramazoline, Tuaminoheptane, Tymazoline, Tyramine, Xylometazoline. ß-ADRENERGIC AGONIST such as Formoterol, Methoxyphenamine, Ritodrine, Terbuterol. α-ARENERGIC BLOKER such as Dapiprazole, Doxazosin, Ergoloid, Mesylates, Fenspiride, Parazosin, Tarazosin, Tolazoline, 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, Dilevalol, Epanolol, Esmolol, Indenolol, Labetalol, Levobunolol, Mepindolol, Metipranolo, Metoprolol, Moprolol, Nadolol, Nadoxolol, Nifenalol, Nipradilol, Oxprenolol, Penbutolol, Pindolol, Practolol, Propranolol, Sotalol, Sulfinalol, Talinolol, 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 Androisoxazole, Androstenediol, Bolandiol, Bolasterone, Clostebol, Ethylestrenol, Formyldienolone, 4-Hydroxy-19-nortestosterone, Methandriol, Methenolone, Methyltrienolone, 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, Dezocine, Diampromide, Dihydrocodeine, Dihydrocodeineone Enol Acetate, Dihydromorphine, Dimenoxadole, Dimepheptanol, Dimethylthiambutene, Dioxaphetyl Butyrate, Dipipanone, Eptazocine, Ethoheptazine, Ethylmethlythiambutene, Ethylmorphine, Etonitazine, Fentanyl, Hydrocodone, Hydromorphone, Hydroxypethidine, Isomethadone, Ketobemidone, Levorphanol, Lofentanil, Meperidine, Meptazinol, Metazocine, Methadone, Metopon, Morphine, Morphine Derivatives, Myrophine, Nalbuphine, Narceine, Nicomorphine, Norlevorphanol, Normethadone, Normorphine, Norpipanone, Opium,Oxycodone Oxymorphone, Papaveretum, Pentazocine, Phenadoxone, Phenazocine, Pheoperidine, Piminodine, Piritramide, Proheptazine, Promedol, Properidine, Propiram, Propoxyphene, Sufentanil, Tilidine. ANALGESIC (NON-NARCOTIC) such as Acetaminophene, Acetaminosalol, Acetanilide, Acetylsalicylates, Acetylsalicylsalicylic Acid, Alclofenac, Alminoprofen, Aloxiprin, Aluminium Bis(acetylsalicylate), Aminochlorthenoxazine, 2-Amino-4-picoline, Aminopropylon, Aminopyrin, Antipyrine, Antipyrine Salicylate, Antrafenine, Apazone, Aspirin, Benorylate, Benoxaprofen, Benzpiperylon, Benzydamine, p-Bromoacetanilide, 5-Bromosalicylic Acid Acetate, Bufexamac, Bucetin, Bumadizone, Butacetin, Carbamazepine, Carbetidine, Carbiphene, Carsalam, Chloralantipyrine, Chlorthenoxazin(e), Cholin Salicylate, Cinchophene, Ciramadol, Clometacin, Cropropamide, Crotethamide, Dexoxadrol, Difenamizole, Diflunisal, Dipyrocetyl, Dipyrone, Emorfazone, Enfenamic Acid, Epirizole, Etersalate, Ethenzamide, Ethoxazene, Etodolac, Felbinac, Fenoprofen, Floctafenine, Flufenamic Acid, Fluoresone, Flupirtine, Fluproquazone, Flurbiprofen, Fosfosal, Gentisic Acid, Glafenine, Ibufenac, Imidazole Salicylate, Indomethacin, Indoprofen, Isofezolac, Isoladole, Isonixine, Ketoprofen, Ketorolac, p-Lactophenetide, Lefetamine, Loxoprofen, Lysine Acetylsalicylate, Methotrimeprazine, Metofoline, Miroprofen, Moraone, Morpholine Salicylate, Naproxen, Nefopam, Nifenazone, 5' Nitro-2' Propoxyacetanilide, Parsalmide, Perisoxal, Phenacetin, Phenazopyridine, Phenocoll, Phenopyrazone, Phenyl Acetylsalicylate, Phenyl salicylate, Phenyramidol, Pipebuzone, Piperylone, Prodilidine, Propacetamol, propyphenazone, Proxazole, Quinine Salicylate, Ramifenazone, Rimazolium, Metilsulfate, Salacetamide, salicin, Salicylamide, O-Acetic Acid, Salicylic Acid, Salicylates and derivatives, Salicylsulfuric Acid, Salsalte, Salverine, Simetride, Sulfamipyrine, Suprofen, Talniflumate, Tenoxicam, Terofenamate, Tetradrine, Tinoridine, Tolfenamic Acid, Tolpronine, Tramadol, Viminol, Xenbucin, Zomepirac ANDROZEN such as Boldenone, Fluoxymesterone, Mestanolone, Mesterolone, Methandrostenolone, 17-Methyitestoserone, 17α -Methyl-testosterone 3-cyclopentyl Enol Ether, Norethandrolone, Normethandrone, Oxandrolone, Oxymetholone, Prasterone, Stanlolone, Stanozolol, Testosterone, Testosterone 17- Chloral Hemiacetal, Testosterone 17-pcypionate, 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, Butanilicaine, Buthalital, Butoxycaine, Carticaine, 2-Chloroprocaine, Cocaethylene, Cocaine, Cyclomethycaine, Cocaethylene, Dibucaine, Dimethisoquin, Dimethocaine, Diperadone, Dyclonine, Ecgonidine, Ecgonine, Ethyl Aminobenzoate, Ethyl Chloride, Etidocaine, Etoxadrol, ß-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, Orthocaine, Oxethazaine, Parethoxycaine, Phenacaine, Phencylidine, Phenol, Piperocaine, Piridocaine, Polidocanol, Pramoxine, Prilocaine, Procaine, Propanidid, Propanocaine, Proparacaine, Propipocaine, Propofol, Propoxycaine, Psedococaine, Pyrocaine, Risocaine, Salicyl Alcohol, Tetracaine, Thialbarbital, Thimylal, Thiobutabarbital, Thiopental, Tolycaine, Trimecaine, Zolamine. ANOREXIC such as Aminorex, Amphecloral, Benzaphetamine, Chlorphentermine, Clobenzorax, Chloforex, Cyclexedrine, Diphemethoxidine, Fenbutrazate, Fenfluramine, Fenproporex, Furfurylmethylamphetamine, Levophacetoperate, Mefenorex, Metamfeproamone, Norpseudoephedrine, Phenpetermine, Picilorex ANTHELMINTIC (CESTODES) such as Arecoline, Aspidine, Aspidinol, Dichlorophen(e), Embelin, Kosin, Napthalene, Niclosamide, Pellertierine, Pellertierine Tannate, Quinacrine. ANTHELMINTIC (NEMATODES) such as Alantolactone, Amoscanate, Ascaridole, Bephenium, Bitoscanate, Carbon Tetrachloride, Carvacrol, Cyclobendazole, Diethylcarbamazine, Diphenane, Dithiazanine Iodide, Dymanthine, Gentian Violet, 4-Hexylresorcinol, Kainic Acid, Mebendazole, 2-Napthol, Oxantel, Piperazines, Pyrantel, Pyrvinium Pamoate, a -Santonin, Stilbazium Iodide, Tetrachloroethylene, Thiabendazole, Thymol, Thymyl Nsoamylcarbamate,Trichlofenol Piperazine, Urea Stibamine, ANTHELMINTIC (ONCHOCERCA) such as Ivermectin ANTHELMINTIC (SCHISTOSOMA) such as Amphotalide, Antimony(s) and Derivatives, Becanthone, Hycanthone, Lucanthone, Niridazole, Oxamniquine, 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, Repirinast, Tiaramide, Tranilast, Traxanox, Urushiol, Cetirizine, Fexophenadine. ANTIAMEBIC such as Arsthinol, Bialamicol, Carbarsone, Cephaeline, Chlorbetamide, Chlorphenoxamide, Dehydroemetine, Dibromopropamidine, Diloxanide, Dephetarsone, Emetine, Fumagillin, Glaucarubin, Glycobiarsol, 8-Hydroxy-7-iodo-5-quinolinesulfonic 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, Ajmaline, Alprenolol, s-Aminoalkyl-s-Arylsulfoximines, Amoproxan, Aprindine, Bretylium Tosylate, Bubumolol, Bunaftine, Butidrine, Butobendine, Capobenic Acid, Cifenline, Disopyramide, Encainide, Flecainide, Hydroquinidine, Indecainide, Ipratopium, Lorajmine, Lorcainide, Meobentine, Mexiletine, Moricizine, Pirmenol, Prajmaline, Procainamide, Pronethalol, Propafenone, Pyrinoline, Quinidine, Quinidine Sulfate, Quinidine, Tocainide, Viquidil. ANTIARTERIOSCLEROTIC such as Pyridinol Carbamate ANTIARTHRITIC/ANTIRHEUMATIC such as Allocupreide Sodium, Auranofin, Aurothioglucose, Aurothioglycanide, Azathioprine, Di-tert-Butyl-phenols, Calcium 3-Aurothio-2-propanol-1-sulfonate, Clobuzarit, Cuproxoline, Diacerein, Glucosamine, Gold Sodium TThiosulfate, Hydroxychloroquine, Kebuzone, Lobenzarit, Melittin, Myoral, Penicillamine ANTIBACTERIAL (ANTIBIOTIC) Aminoglycosides such as Amikacin, Apramycin, Arbekacin, Bambermycins, Butirosin, Dibekacin, Dihdrostreptomycin, Fortimicin(s), Fradiomycin, Gentamicin, 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 ß-Lactams Carbapenems such as Imipenem Cephalosporins, such as l-Carba(dethia) Cephalosporin, Cefactor, Cefadroxil, Cephalosporins, Cefatrizine, Cefazedone, Cefazolin, Cefexime, Cefmenoxime, Cefodizime, Cefonicid, Cefoperazone, Ceforanide, Cefotaxime, Cefotiam, Cefmizole, Cefpirimide, Cefpodoxime Proxetil, Cefroxadine, Cefsulodin, Ceftazidime, Cefteram, Ceftezole, Ceftibuten, Ceftizoxime, Ceftriaxone, Cefuroxime, Cefuzonam, Cephacetrile, Sodium, Cephalexin, Cephaloglycin, Cephaloridine, Cephalosporin, Cephalothin, Cephapirin Sodium, Cephradine, Pivcefalexine Cephamycin such as Cefbuperazone, Cefmetazole, Cefminox, Cefetan, Cefoxitin Manobactams such as Aztreonam, carumonam, Tigemonam Oxacephems such as Flomoxef, Moxolactam Penicillins such as Amidinocillin, Amdinocillin, Pivoxil, Amoxicillin, Ampicillan, Apalcillin, Aspoxicillin, Azidocillan, Azlocillan, Bacampicillin, Benzylpenicillinic Acid, Benzylpenicillin, Carbenicillin, Carfecillin, Carindacillin, Clometocillin, Cloxacillin, Cyclacillin, Dicloxacillin, Diphenicillin, Epicillin, Fenbenicillin, Floxicillin, Hetacillin, Lenampicillin, Metampicillin, Methicillin, Mezlocillin, Nafcillin, Oxacillin, 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 O, Penicillin v, Penicillin V Benzathine, Penicillin V Hydrabamine, Penimepicycline, Phenethicillin , Piperacillin , Pivapicillin , Propicillin , Quinacillin, Sulbenicillin, Talampicillin, Temocillin, Ticarcillin Lincosamides such as clindamycin, Lincomycin Macrolides such as Azithromycin, Carbomycin, Clarithromycin, Erythromycin(s) and Derivatives, Josamycin, Leucomycins, Midecamycins, Miokamycin, Oleandomycin, Primycin, Rosaramicin, Roxithromycin, Spiramycin, Troleandomycin, Polypeptides such as Amphomycin, Bacitracin, Capreomycin, Colistin, Enduracidin, Enviomycin, Fusafungine, Gramicidin(s), Gramicidin S, Mikamycin, Polymyxin, Polymyxin B-Methanesulfonic, Acid, Pritinamycin, Ristocetin, Teicoplanin, Thiostrepton, Tuberactinomycin, Tyrocidine, Tyrothricin, Vancomycin, Vimomycin(s), Virginiamycin, Zinc Bacitracin Tetracyclines such as Apicycline, Chlortetracycline, Clomocycline, Demeclocycline, Guamecycline, Lymecycline, Meclocycline, Methacycline, Minocycline, Oxytetracycline, Penimepicycline, Pipacycline, Rolitetracycline, Sancycline, Senociclin, Tetracycline Others Such as Cycloserine, Mupirocin, Tuberin ANTIBACTERIAL (SYNTHETIC) 2,4-Diaminopyrimidines such as Brodimoprim, Tetroxoprim, Trimethoprim Nitrofurans such as Furaltadone, Furazolium, Nifuradene, Nifuratel, Nifurfoline, Nifurpirinol, Nifurprazine, Nifurtoinol, Nitrofurantoin Quinolones and Analogs such as Amifloxacin, Cinoxacin, Ciprofloxacin, 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, Formosulfathiazole, N2-Formyl-Sulfisomidine, N4-ß-D-Glucosysulfanilamide, Mafenide, 4'-(Methyl-sulfamoyl) sulfanilanilide, p-Nitrosulfathiazole, Noprysulfamide, Phthalysulfacetamide, Phthalysulfathiazole, Salazosufadimidine, Succinylsulfathiazole, Sulfabenzamide, Sulfacetamide, Sulfachlorpyridazine, Sulfachrysoidine, Sulfacytine, Sulfadiazine, Sulfadicramide, Sulfadimethoxine, Sulfadoxine, Sulfaethidole, Sulfaguanidine, Sulfaguanol, sulfalene, Sulfaloxic Acid, Sulfamerazine, Sulfameter, Sulfamethazine.Sulfamethizole, Sulfamethomidine, Sulfamethoxazole, Sulfamethoxypyridazine, Sulfametrole, Sulfamidochrysoidine, Sulfamoxole, Sulfanilamide, Sulfanilamidomethanesulfonic Acid, Triethnolamine Salt, 4-Sulfanilamidosalycylic Acid, N4-SulfanilySulfanilamide, Sulfanilyurea, N-Sulfanilyl-3,4-xylamide, Sulfanitran, Sulfaperine, Sulfaphenazole, Sulfaproxyline, Sulfapyrazine, Sulfapiridine, Sulfasomizole, Sulfasymazine, Sulfathiozole, Sulfathiourea, Sulfatolamide, Sulfisomidine, Sulfisoxazole Sulfones such as Acedapsone, Acediasulfone, Acetosulfone, Dapsone, Diathimosulfone, Glocosulfone, Solasulfone, Succisulfone, Sulfanilic Acid, p-sulfanilylbenzyllamine, p,p'-sulfonyldianiline,-N,N'digalactoside, Sulfoxone, Thiazolesulfone Others such as Clofoctol, Hexedine, Magainis, Methenamine Anhydromethylene-citrate, Methenamine Hippurate, Methenamine Mandelate, Methenamine Sulfosalicylate, Nitroxoline, Squalamine, Xibornol ANTICHOLINERGIC such as Adiphenine, Alverine, Ambutonomium, Aminopentamide, Amixetrine, Amprotropine Phosphate, Anisotropine, Methylbromide, Apoatropine, Atropine, Atropine N-Oxide, Benactyzine, Benapryzine, Benzetimide, Benzelonium, Benztropine, Mesylate, Bevonium Methyl Sulfate, Biperiden, Butropium N-Butylscopolammonium Bromide, Buzepide, Camylofine, Caramiphen, Chlorbenzoxamine, Chlorphenoxamine, Cimetropium, Clidinium, Cyclodrine, Cyclonium, Cyclopentolate, Cycrimine, Deptropine, Dexitimide, Dibutoline sulfate, Dicyclomine, Diethazine, Difemerine, Dihexyverine, Diphemanil, Methylsulfate, N-(1,2-Dipheylethyl)nicotinamide, Dipiprovrine, Diponium, Emepronium, Endobenzyline, Ethopropazine, Ethybenztropine, Ethylbenzhydramine, Etomidoline, Eucatropine, Fenpiverinium, Fentonium, Flutropium, Glycopyrrolate, Heteronium, Hexocyclium Methyl Sulfate, Homatropine, Homatropine Methyl Bromide, Hyoscyamine, Ipratropium, Isopropamide, Levomepate, Mecloxamine, Mepenzolate, Metcaraphen, Methantheline, Methixene, Methscopolamine, Octamylamine, Oxybutynin, Oxyphencyclimine, Oxyphenonium, Pentapiperide, Penthienate, Phencarbamide, Phenglutarimide, Pipenzolate, Piperidolate, Piperilate, Poldine Methysulfate, Pridinol, Prifinium, Propyromazine, Scopolamine N-Oxide, Stilonium, Stramonium, Sultroponium, Thihexinol, Thiphenamil, Tiemonium, Timepidium, Tiquizium, Tridihexethyl Iodide, Trihexyphenidyl, Hydrochloride, Tropacine, Tropenzile, Tropicamide, Trospium, Valethamate, Xenytropium ANTICONVULSANT such as Acetylpheneturide, Albutoin, Aloxidone, Aminoglutethimide, 4-Amino-3-hydroxybutyric Acid, Atrolactamide, Beclamide, Buramate, Carbamazepine, Cinromide, Clonazepam, Decimemide, Diethadione, Dimethadione, Doxenitoin, Eterobarb, Ethadione, Ethosuximide, Ethotoin, Fluresone. 5-Hydroxytryptophan, Lamotrigine, Magnesium Sulfate, Mephenytoin, Metharbital, Methetoin, Methsuximide, 5-Methyl-5-(3-phenanthryl)-hydantoin, 3-Methyl-5-phenylhydantoin, Narcobarbital, Nimetazepam, Nitrazepam, Paramethadione, Phenacemide, Pheneturide, Phensuximide, Phenytoin, Phethenylate Sodium, Primidone, Progabide, Solanum, Strontium, Suclofenide, Sulthiame, Tetrantoin, Trimethadione, Valproic Acide, Valpromide, Vigabatrine, Zonisamide. ANTIDEPRESSANT Bicyclics such as Binedaline, Caroxazone, Citalopram, Dimethazan, Indalpine, fencamine, Indeloxazine, Nefopam, Nomifensine, Oxitriptan, Oxypertine, Paroxetine, Sertraline, Thiazesim, Trazodone, Zometapine, Hydrazides/Hydrazines such as Benmoxine, Iproclozide, Iproniazid, Isocarboxazid, Nialamide, Ictamoxine, Phenelzine. Pyrrolidones such as Continine, Rolicyprine, Rolipram. Tetracyclics such as Maprotiline, Metralindole, Mianserine, Oxaprotiline. Tricyclics such as Adinazolam, Amitriptyline, Amitriptylinoxide, Amoxapine, Butriptyline, Clomiparamine, Demexiptiline, desiparamine, Dibenzepin, Dimetracrine, Dothiepin, Doxepin, Fluacizine, Imipramine, Imipramine N-Oxide, Iprindole, Lofepramine, Melitracen, Metapramine, Nortriptyline, Noxiptilin, Opipramol, Propizepine, Protriptyline, Quinupramine, Tianeptine, trimiparamine. Others such as Benactyzine, Bupropin, Butacetin, Deanol, Deanol Aceglumate, Deanol Acetamidebenzoate, Dioxadrol, etoperidone, Febarbamate, Femoxetine, Fenpentadiol, Fluoxetine, Fluvoxamine, Hematopotphyrin, Hypercinin, Levophacetoperane, Lithium, Medifoxamine, Minaprine, Moclobemide, Oxaflozane, Piberaline, Polycyclic Imides, Prolintane, Pyrisuccideanol, Rubidium, Sulpiride, Sultopride, Teniloxazine, Thozalinone, Tofenacin, Toloxatone, Tranylcypromine, L-Tryptophan, Viloxazine, Zimeldine. ANTIDIABETIC Biguanides such as Buformine, Metformin, Phenformin. Sulfontlurea Derivatives such as Acetohexamide, 1-Butyl-3-metanilylurea, Carbutamide, Chlorpropamide, Glibornuride, Gliclazide, Glipizide, Gliquidone, Glisoxepid, Glyburide, Glybuthiazol(e), Glybuzole, Glyhexamide, Glymidine, Glypinamide, Phenbutamide, Tolazamide, Tolbutamide, Tolcyclamide. Others such as Acarbose, Benzylthiazolldone-2,4-dione, Calcium Mesoxalate, Miglitol. ANTIDIARRHEAL such as Acetyltannic Acid, albumin Tannate, Alkofanone, Aluminium Salicylates, Catechin, Difenoxin, diphenoxylate, Lidamidine, Loperamide, Mebiquine, Trillium, Uzarin. ANTIDIURETIC such as Desmopressin, felypressin, Lypressin, Ornipressin, Oxcinchophen, Terlipressin, Vasopressin. ANTIESTROGEN such as Delmadione Acetate, Ethamoxytriphetol, Tamoxifen, Toremifene. ATRIFUNGAL (ANTIBIOTICS) Polyenes such as Amphotericin-B, Canadicidin, Dermostatin, Filpin, Fungichromin, Hachimycin, Hamycin, Lucensomycin, Mepartricin, Natamycin, Nystatin, Pecilocin, Perimycin. Others such as Azaserine, Griseofulvin, Oligomycins, Pyrrolnitrin, 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, Bromosalicylchloranilide, Buclosamide, Chlophenesin, Ciclopirox, Cloxyquin, Coparaffinate, Diamthazole, Dihydrochloride, Exalamide, Flucytosine , Halethazole, Hexetidine, Loflucarbon, Nifuratel, Potassium Iodide, Propionates, Propionic Acid, Pyrithione, Salicylanilide, Sulbentine, Tenonitrozole, Tolciclate, Tolindate, Tolnaftate.Tricetin, 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 Acrivastine, Bamipine, Brompheniramine, Chlorpheniramine, Dimethindede, Tolpropamine, Triprolidine Aminoalkyl Ethers such as Bietabautine, Bromodiphenhydramine, Carbinoxamine, Clemastine, Diphenlypyraline, Doxylamine, Embrammine, Medrylamine, Mephenphydramine, p-Methyldiphenhydramine, Orphenadrine, Phenyltoloxamine, Piprinhydrinate, Setasine Ethylenediamine Derivatives such as Alloclamide, p-Bromtripelennamine, Chloropyramine, Chlorothen, Histapyrrodine, Methafurylene, Methaphenilene, Methapyrilene, Phenbenzamine, Pyrilamine, Talastine, Thenyldiamine, Thozylamine, Tripelennamine, Zolamine Piperazines such as Cetirizine, Chlorcyclizine, Clocinizine, Hydroxyzine Tricyclies Phenothiazines such as Ahistan, Etymemazine, Fenethazine, N-Hydroxyethylpromethazine, Isopromethazine, Mequitaz inc, Promethazine, Pyrathiazine, Thiazinamium Methyl Sulfate Others such as Azatadine, Clobenzepam, Cyproheptadine, Deptropine, Isothipendyl, Loratadine, Prothipendyl Others such as Antazoline, Cetoxime, Clemizole, Clobenztropine, Diphenazoline, Diphenhydramine, Mebhydroline, Phenindamine, Terfenadine, Tritoqualine Antihyperlipoproteinemic Aryloxyalkanoic Acid Derivatives such as Bazafibrate, Binifibrate, Ciprofibrate, Clinofibrate, Clofibrate, Clofibric Acid, Etonfibrate, Fenofibrate, Gemfibrozil, Nicofibrate, Pirifibrate, Ronifibrate, Simfibrate, Theofibrate Bile Acid Sequesterants such as Cholestyramine Resin, Colestipol, Polidexide HMG CoA Reductass Inhibitors such as Lovastatin, Pravastatin, Simvastatin Nicotinic Acid Derivatives Aluminium Nicotinate, Acipimox, Niceritol, Nicoclonate, Nicomol, Oxiniacic Acid Thyroid Hormones/Analogs such as Etiroxate, thyropropic Acid Others such as Acifran, Azacosterol, Benfluorec, (3-Benzalbutyramide, Benzodioxole, Carnitine, Chondroitin Sulfate, Clomestone, Detaxtran, Dextran Sulfate Sodium, 5,8,11,14,17-Eicosapentaenoic Acid, Eritadenine, Farnesylated tetrahydro-naphthalenols, Furazbol, Meglutol, Melinamide, Mytatrienediol, Naphtyl- tetrahydronaphtyl - diphosphonates, Ornithine, y-Oryzanol, Pentethine, Penataerythritol, Tetraacetate, a-Phenylbutyramide, Phylate Acids and Salts, Pirozadil, Probucol, a-Siosterol, Sultosilic Acid, Tiadenol, Triparanol ANTIHYPERTENSIVE Benzothiadiazine Derivatives sich as Althiazide, Bendroflumethiazide, 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 Alacepril, Captopril, Cilazapril, Enalapril, Enalaprilat, Fosinopril, Lisinopril, Moveltipril, Perindopril, Quinapril, Ramipril Guanidine Derivatives Bethanidine, Debrisoquin, 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 Quanternary Ammonium Compounds Azamethonium Chlorisondamine, Hexamethonium, Pentacynium, Bis(methylsulfate), Pentamethonium, Pentolinium Tartate, Phenactopinium, Trimethidiunum Methosulfate Quinazoline Derivatives such as Alfuzosin, Bunazosin Reserpine Derivatives such as Bietaserpine, Deserpidine, Rescinnamine, Reserpine, Syrosingopine Sulfanoamide Derivatives such as Ambuside, Clopamide, Furosemide, Indapamide, Quinethazone, Tripamide, Xipamide Others such as Aimaline, g-Aminobutyric Acid, Bufeniode, Chlorthalidone, Cicletaine, Ciclosidomine, Cryptenamine Tannates, Flosequinan, Indoramin, Ketanserin, Metbutamate, Mecamylamine, Methyldopa, Methyl 4-Pyridyl Ketone Thiosemicarbarzone, Metolazone, Minoxidil, Muzolimine, Pargyline Glycine Aminopropargyl Diols, Protoveratrines, Raubasine, Rescumetol, Saralasin, Sodium Nitroprusside, Ticrynafen, Trimethaphan Camsylate, Tyrosinase, Urapidil ANTIHYPERTHYROID such as 2-Amino-4-methyl-thiazole, 2-Aminothiazole, Carbimazole, 3,5-Dibromo-L-tyrosine, 3,5-Diiodotyrosine, Hinderin, Iodine, lothiouracil, Methimazole, Methylthiouracil, Propylthiouracil, Sodium Perchlorate, Thibenzazoline, Thiobarbital, 2-Thiouracil ANTIHYPOTENSIVE such as Amezinium Methyl Sulfate, Angiotensin Amide, Etifelmin, Etilefrin, Gepefrine ANTIHYPOTHYROID such as Levothyroxine, Liothyronine, Thyroid, Thyroidin, Thyroxine, Tiratricol ANTI-INFLAMMATORY (NONSTEROIDAL) Aminoarylcarboxylic Acid Derivatives such as Etofenamate, Meclofenamic Acid, MefanamicAcid, NiflumicAcid Arylacetic Acid Derivatives such as Acemetacin, Amfenac, Cinmetacin, Clopirac, Diclofenac, Fenclofenac, Fenclorac, Fenclozic Acid, Fentiazac, Glucametacin, Isoxepac, Lonazolac, Metiazinic Acid, Oxametacine, Proglumetacin, Sulindac, 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, Pranoprofen, Protizinic Acid, Tiaprofenic Acid Pyrazoles such as Mepirizole Pyrazolones such as Clofezone, Feprazone, Mofebutazone, Oxyphenbutazone, Phenylbutazone, Phenyl Pyrazolidininones, Suxibuzone, Thiazolinobutazone 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-Amino-4-hydroxybutyric Acid, Amixetrine, Bendazac, Bucolome, Carbazones, Difenpiramide, Ditazol, Guaiazulene, Heterocyclic Aminoalkyl Esters of Mycophenolic Acid and Derivatives, Nabumetone, Nimesulide, Orgotein, Oxaceprol, Oxazole Derivatives Paranyline, Pifoxime, 2-substituted-4, 6-di-tertiary-butyl-s-hydroxy-1,3-pyromidines, Proquazone, Sialyl Lewisx Dimers, Tenidap ANTI MALARIAL such as Acedapsone, Alphaaminoquinolines, 40Aminoquinolines, Amodiaquin, Arteether.Artmether, Artemisinin, Artesunate, Bebeerine, Chirata, Chlorguanide, Chloroquine, Chloproguanil, Cinchone, Cinchonidine, Cinchonine, Cycloguanil, Euquinine, Gentiopicrin, Halofantrine, Mefloquine Hydrochloride, 3-Methylarsacetin, Pamaquine, Plasmocid, Primaquine, Pyrimethamine, Quinacrine, Quinine, (Acids, Salts and Derivatives), Quinine Formate, Quinine Gluconate, Quinine Tannate, Quinine Urea Hydrochloride, Quinocide, Quinoform, Quinoline, Sodium Arsenate, Diabasic ANTIMIGRAINE such as Akpiropride, Dihydrergotamine, Ergocornine, Ergocorninine, Ergocryptine, Ergot, Ergotamine, Flumedroxone Flumedroxone, Acetae, Fonazine, Methysergid(e), Oxetorone, Pizotyline, Sumatriptan ANTINAUSEANT such as Acetylleucine Monoethanolamine, Bietanautine, Bromopride, Buclizine, Clebopride, Cyclizine, Dimenhydrinate, Diphenidol, Domperidone, Gransetron, Meclizine, Methaltal, Metoclopramide, Metopimazine, Nabilone, Ondansteron, Oxypendyl, Pipamizine, Piprinhydrinate, Scopolamine, Tetrahydrocannabinols, Thiethylperazine, Trimethobenzamide ANTIMEOPLASTIC Alkyl agents : Alkyl Sulfonates such as Busylfan, Improsulfan, Piposulfan Aziridines such as Benzodepa, Carboquone, Meturedepa, Uredepa Ethylenimines and Methylmelamines such as Altretamine, Triethylenemelamine, Triethylenephosphoramide, Triethylenethiophosphoramide, Trimethylolomelamine Nitrogen Mustards such as Chlorambucil, Chlornaphazine, Chclophosphamide, Chclophosphamide, Estramustine, Ifosfamide, Mechlorethamine, Mechlorethamine Oxide Hydrochloride, Melphalan, Novembichin, Phenesterine, Prednimustine, Trofosfamide, Uracil Mustard Nitrosoureas Carmustine, Chlorozotocin, Fotemustine, Lomustine, Nimustine, Ranimustine Others such as Dacrabazine, Mannomustine, Mitobronitol, Mitolactol, Pipobroman Antibiotics such as Aclacinomycins, Actinomycin F1, Anthramycin, Azaserine, Bleomycins, Cactinomycin, Carubicin, Carzinophilin, Chromomycins, Dactinomycin, Daunorubicin. 6-Diazo-5-oxo-L-naroleucine, Doxorubicin, Epirubicin, Mitomycins, Mycophenolic Acid, Nogalamycin, Olivomycins, Peplomycin, Plicamycin, Porfiromycin, Puromycin, Streptonigrin, Streptozocin, Tubercidin, Ubenimex, Zinostatin, Zorubicin Antimetabolites Folic Acid Analogs such as Denepterin, Methotrexate, Pteropterin, Trimetrexate Purine Analogs such as Fludarabine, 6-Mercaptopurine, Thiamiprine, Thiguanaine Pyrimidine Analogs such as Ancitabine, Azacitidine, 6-Azauridine, Carmofur, Cytarabine, Didexyuridines, Doxifluridine, Enocitabine, floxuridine, Fluororacil, Tegafur Enzymes such as L-Asparaginase, Pulmozyme Others such as Aceglatone, Aldophophamide Glycoside, Aminolevulinic Acid, Amsacrine, Bestabucil, Bisantrene, Carnoplarin, Deformide, Demecolcine, Diaziquone, Elfornithine, Elliptinium Acetate, Etoglucid, Etoposide, Gallium Nitrate, Hydroxyurea, Interferon-a, Interferon-p, Interferon-y, lnterleukine-2, Lentinan, Lonidamine, Mitoguazone, Mitoxantrone, Mopidamol, Nitracrine, Pentostatin, Phenamet, Pirarubicin, Podophyllinicc Acid, 2-Ethythydrazide, Procarazine, PSK®, Razoxane, Sizofiran, Spirogermanium, Taxol, Teniposide, Tenuazonic Acid, Triaziquone, 2,2',2"-Trichlorotriethylamine, Urethan, Vinblastine, Vincristine, 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)-lmidazoles ANTINEOPLASTIC ADJUNCT Folic Acid Replenisher such as Frolinic Acid ANTIPARKINSONIAN such as Amantadine, Benserazide, Bictanaurine, Biperiden, Budipine, Carbidopa, deprenyl, Dexetimide, Diethazine, Droxidopa, Ethopropazine, Ethylbenzhydtamine, Levodopa, Piroheptine, Pridinol, 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, Melarsoprol, Mifutrimox, Oxophenarsine, Puromycin, Quinapyramine, Suiramin Sodium, Trypan Red, Tryparasmide ANTIPRURITIC such as Camphor, Cyproheptadine, Dichlorisone, Glycine, Halometasone, 3-Hydroxycamphor, Menthol, Mesulphen, Methdilazine, Phenol, Spirit of camphor, Trimeprazine ANTIPSORLATIC such as Acitretin, Anthralin, 6-Azauridine, Bergapten(e), Chrysarobin, Eoretinate, Pyrogallol ANTIPSYCHOTIC Butyrophenones such as Benperidol, Bromperidol, Droperidol, Fluanisone, Haloperidol, Melperone, Moperone, Pipamperone, Sniperone, Timiperone, Trifulperidol Phenothiazines such as Acetophenazine, Bhutaperazine, Carphenazine, Chlorproethiazine, Chlorpromazine, Clospirazine, Mepazine, Mesoridazine, Methoxypromazine, Metofenazate, Oxaflumazine, Perazine, Pericyazine, Perimethazine, Perchloperazine, Promazine, Sulforidazine, Thiopropazate, thioridaziane, Trifluoperazine, Triflupromazine Thioxanthenes such as Chlorprothixene, Clopenthixol, Flupentixol, Thiothixene Other such as Alizapride, Amisulpride, 4-Arylpiperazines, 4-Arypiperdines, Buramate, Fluspirilene, Moledone, Penfluridol, Pimozide, Spirilene, Sulpiride ANTIPYRETIC such as Aconine, Aconite, Aconitine, Phenicarbazide ANTIRICKETTSIAL such as p-Aminobenzoic Acid ANTISEBORRHEIC such as 3-O-Lauroylpyridoxol Diacetate, Piroctone, Resorcinol, Selenium Sulfides, Tioxolone ANTISEPTIC Guanidines such as Alexidine, Ambazone, Chlorhexidine, Picloxydine Halogens/Halogen Compounds such as Bronyl Chloride, Calcium lodate, Iodine Monochloride, Iodine Trichloride, lodoform, Povidone-lodine, Sodium Hyopchlorite, Sodium lodate, Symclosene, Thymol Iodide, Triclocarban, Triclosan, Troclosene Potasium Nitrofurnase such as Flrazolidone, 2-(Methoxymethyl)-5-Nitrofuran, Nidroxyzone, Nifuroxime, Nifurzide, Nitrofurazone Phenols such as Acetomeroctol, Chloroxylenol, Hexachlorophene, 1-Napthyl Salicylate, 2,4,6-Tribromo-m-cresol, 3',4',5-Trichlorosalicylanilide Quinolines such as Aminoquinuride, Chloroxine, Chlorquinadol, Cloxyquin, Ethylhydrocupreine, Halquinol, Hydrastine, 8-Hydroxquinoline Sulfate Others such as Boric Acid, Chloroazodin, m-Cresyl Acetate, Cuperic Sulfate, Ichthammol ANTISPASMODIC such as Alibendol, Ambucetamide, Aminopromazine, Bietamiverine, Butaverine, Butropium, Carverine, Cimetropium, Cinnamedrine, Clebopride, Confine Hydrobromide, Coniine, Difemerine, Diisopromine, Dioxaphetyl Butyrate, Drofenine, Ethaverine, Feclemine, Fenalamide, Fenoverine, Fenpiprane, Flavoxate, Flopropione, Gluconic Acid, Guaiactamine, Hydramitrazine, Hymecromone, Leiopyrrole, Mebeverine, Moxaverine, Nafiverine, Octaverine, Phenamacide, Phloroglucinol, Pinaverium, Piperilate, Pipoxolan Hydrochloride, Pramiverin, Properidine, Propivane, Propyromazine, Prozapine Racefemine, Rociverine, Spasmolytol, Stilonium, Tiropramide, Trepibutone, Tricromyl, Trifolium, Trimebutine, N, N-1 Trimethyl-3, 3-diphenylpropylamine. ANTITHROMBOTIC such as Anagrelide, Argatroban, Cilostazol, Daltroban, Defibrotide, Enoxaparin, Fraxipariner®, Indobufen, Lamoparan, Ozagrel, Picotamide, Plafibride, Tedelparin, Ticlopidine, Triflusal. ANTITUSSIVE such as Allocamide, Amicibone, Benproperine, 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-Diphenyl-2-piperidinepropanol, Dropropizine, Drotebanol, Eprazinone, Ethyl Dibunate, Ethylmorphine, Fominoben, Guiaiapate, Hydrocodone, Isoaminile, Levopropoxyphene, Morclofone, Narceine, Normethadonem Noscapine, Oxeladin, Oxolamine, Pholcodine, Picoperine, Pipazethate, Piperidione, Prenoxdiazine, Racemethorphan, Taziprinon Hydrochloride, Tipepidine, Zipeprol. ANTITULCERATIVE such as Aceglutamide Aluminum, Complex, ε-Acctamidocaproio Acid Zinc Salt, Acetoxolone, Arbaprostil, Benexate Hydrochloride, Bismuth Subcitrate Sol (Dried), Carbenoxolone, Cetraxate, Cimetidinc, Enprostil, Esaprazole, Famotidine, Raxilide, Gefarnate, Guaiazulene, Irsogladine, Nizatidine, Omeprazole, Ornoprostil, γ-Oryzanol, Pifarnine, Pirenzepine, Plaunotol, Ranitidine, Rioprostil, Rosaprostol, Rotraxate, Roxatidine Acetate, Sofaicone, Spizofurone, Sucralfate, Teprenone, Trimoprostil, Thrithiozine, Troxipide, Zolimidine. ANTIUROLITHIC such as Acetohydroxamic Acid, Allopurinol, Potassium Citrate, Succinimide. ANTIVENIN such as Lyovacr®, Antivenin. ANTIVIRAL Purines/Pyrimidinones such as 2-Acetyl-pyridine 5-((2-pyridylamino) thiocarbonyl), Thiocarbonohydrazone, Acyclovir, Dideoxyadenosine, Dideoxycytidine, Dideoxyinosine, Edoxudine, Floxuridine, Ganciclovir, Idoxuridine, MADU, Pyridinon, Trifluridine, Vidrarbine, Zidovudine. Others such as Acetylleucine Monoethanolamine, Acridianamine, Alkylisooxazoles, Amantadine, Amidinomycin, Cuminaldehyde Thiosemicarbzone, Foscarnet Sodium, Kethoxal, Lysozyme, Methisazone, Moroxydine, Podophyllotoxin, Ribavirin, Rimantadine, stallimycin, statolon, Thymosins, Tromantadine, Xenazoic Acid. ANXIOLYTIC 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, Suriclone. BENZODIAZEPINE ANTAGONIST such as Flumazenil. BRONCHODILATOR Ephedrine Derivatives such as Albuterol, Bambuterol, Bitolterol, Carbuterol, Clenbuterol, Clorprenaline, Dioxethedrine, Eprozinol, Etafedrine, Ethylnorepinephrine, Fenoterol, Hexoprenaline, Isoetharine, Isoproterenol, Mabuterol, Metaproterenol, N-Methylephedrine, Pirbuterol, Procaterol, Protokylol, Reproterol, Rimiterol, Soterenol, Terbutaline, 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, Guaithylline, Proxyphylline, Theobromine, 1-Theobromineaceatic Acid, Theophylline. Others such as Methoxyphenanime, Tretoquinol. CALCIUM CHANNEL BLOCKER Arylalkylamines such as Bepridil, Ditiazem, Fendiline, Gallopamil, Terodiline, Verapamil. Dihydropyridine Derivatives such as Felodipine, Isradipine, Nicardipine, Nifedipine, Nilvadipine, Nimodipine, Nisoldine, Nitrendipine. Piperazine Derivatives such as Flunarisine. Others such as Perhexiline. CALCIUM REGULATOR such as Calcifediol, Calcitonin, Calcitriol, Clodronic Acid, Dihydrotachysterol, Elcatonin, Etidronic Acid, Ipriflavone, Pamidronic Acid, Parathyroid Hormone, Teriparatide Acetate. CARDIOTONIC such as Acetyldigititoxins, 2-Amino 4-picoline, Amrinone, Buclasdesine, cerberoside, Camphotamide, Convallatoxin, Cymarin, Denopamine, Deslanoside, Ditalin, Digitalis, Digitoxin, Digoxin, Dobutamine, Dopamine, Dopexamine, Enoximone, Erythrophleine, Fenalcomine, Gitalin, Gitoxin, Glycocyamine, Heptaminol, Hydrastinine, Lanotodises, Metamivam, Substituted Methoxyphenyl-4, 5-dihydro-3(2H)-pridazinones, Milrionone, Neriifolin, Oleandxin, Ouabain, Oxyfedrine, Prenalterol, Proscillaridin, Resibufogenin, Scillaren, Scillarenin, Strophanthin, Sulmazole, Theobromine, Xamoterol. CHELATING AGENT such as Deferozmine, Edetate Calcium Disodium, Edetate Disodium, Edeate Sodium, Edetate Trisodium, Pentetate Calcium Trisodium, Pentectic Acid, Succimer, Trientine. CHOLECYSTOKININ ANTAGONIST (CCK Antagonist) CHOLELITHOLYTIC AGENT such as Chenodiol, Methyl tert-Butyl Ether, Monooctanoin, Ursodiol. CHOLERETIC such as Alibendol, Anethole Trithion, Azintamide, Cholic Acid, Cicrotoic Acid, Clanobutin, Cyclobutyrol, Cyclovalone, Cynarin(e), Dehydrocholic Acid, Deoxycholic Acid, Dimecrotic Acid, ?-Ethylbenzyl Alcohol, Exiproben, Feguprol, Fencibutirol, Fenipentol, Florantyrone, hymecromone, Menbutone, 3-(O-Methoxyphenyl)-2-phenylacrylic Acid, Metochalcone, Moquizone, Osalmid, Ox Bile Extract, 4, 4'-Oxydi-2-butanol, Piprozolin, Prozapine, 4-Salicyloylmorpholine, Sincalide, Taurocholic Acid, Timonacic, Tocamphyl, Trepibutone, Vanitiolide. CHOLINERGIC such as Aceclidine, Acetylcholine, Acetylcholide, Aclatonium Napadisilate, Benzpyrinium Bromide, Bethanechol, Carbachol, Carpronium, Demecarium, Dexpanthenol, Diisopropyl Paraoxon, Echothiophate, Edrophomium, Eseridine, Furtrethonium, Isoflurophate, Methacholine Chloride, Muscarine Neostigmine, Oxapropanium, Physostigmine, Pyridostigmine. CHOLINESTERASE INHIBITOR such as Ambenonium, Distigmine, Galanthamine. CHOLINESTERASE REACTIVATOR such as Obidoximine, Pralidoxime CNS STIMULANT/AGENT such as Amineptine, Amphetimine, Amphetaminil, Bemegride, Benzphetamine, Brucine, Caffeine, Chlorphentermine, Cloferciclan, Cloratermine, Coca, Demanyl Phosphate, Dexoxadrol, Dextroamphetamine Sulfate, Diethlpropion, N-Ethylamphetamine, Ethamivan, Etifelim, Etryptamine, Fencamfamine, Fenethylline, Fenosolone, Flurothyl, Hexacyclonate Sodium, homocamfin, Mazindol, Megexamide, Methamphetamine, Methylphenidate, Nicotine, Nicorinic Agonist, Nikethamide, Pemoline, Pentylenetetrazole, Phenidimetrazine, Phenmetrazine, Phentermine, Picrotoxin, Pipradrol, Prolintane, Pyrovalerone, Terahydrobenzothienpphyridines. DECONGESTANT such as Cafaminol, Nordefrin DENTAL CATTIES PROPHYLACTIC such as Sodium Fluoride. DEPIGMENTOR such as Hydroquinine, Hydroquinone, Monobenzone. DIURETIC Organomercurials such as Chlormerodrin, Meralluride, Mercamphamide, Mercaptomerin Sodium, Mercumallyic Acid, Mercumatilin Sodium, Mercurous Chloride, Mersalyl. Pteridines such as Furterence, Triamterene. Purines such as 7-Morpholinomethyltheophylline, Pamabrom, Protheobromine, Theobromine Steroids such as Canrenone, Oleandrin, Spironolactone Sulfonamide Derivatives such as Acetazolmide, Azosemidem, Bumetanide, Butazolamide, Chloraminophenamide, Clofenamide, Clorexolene, Diphenylmethane-4, 4'-disulfonamide, Disulfamide, Ethoxzolamide, Flumethiazide, Mefruside, Methazolamide, Piretanide Torasemide. Uracils such as Aminometradine, Amisometradine Others such as Amanozine, Amiloride, Arbutin, Chlorazanil, Ethacrynic Acid, Etozolin, Isosorbide, Mannitol, Metochalone, Pethexiline, Urea. DOPAMINE RECEPTOR AGONIST such as Bromocriptine, Fenoldopam, Lisuride, Naxagolide, Pergolide. 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(Swine Pancreas), Lipase, Pancrelipase, Pepsin, Rennim Penicillin Inactivating such as Penicillinase Proteolytic such as Collagenase, Chymopapain, Chymotrypsins, Papain, Trypsin. ENZYME INDUCER (HEPATIC) such as Flumecinol. ESTROGEN Nonsteroidal such as Benzestrol, Broparoestrol, Chlorotrianisene, Dienestrol, Diethyistilbestrol, Diethyistilbestrol Diproprionate, Dimestrol, fosfestrol, Hexestrol, Methallenstril, Methestrol. Steroidal such as Colpormon, Conugated Estrogenic Hormones, equilenin, Equilin, Esterified Estrogens Esteropipate, 17b-Estradiol, estradiol, Estradiol Benzoate, Estradiol 17b-Cypionate, Estrone, Ethibyl Estradiol, Mestranol, Moxestrol, Mytatrienediol, Polyestradiol Phosphate, Quinestradiol, Quinestrol. GASTRIC SECRECTION INHIBITOR such as enterogastrone, Octreotide. GLUCOCORTICOID such as 21-Acetoxyprefnenolone, Aalclometasone, Algestone, Amicinonide, Beclomethasone, Betamethasone, Betamethasone Dipropionate, Budesonide, Chloroprednisone, Clobetasol.Blovetasone, 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, Flurandrenolide, 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-Diethylaminoacerate, Prednisone Sodium Phosphate, Prednisolone Sodium Succinate, Prednisolone Sodium 21 -m-Sulfobenzoate, Prednisolone 21-Stearoylglycolate, Prednisolone Tebutatem Orednisolone 21-Trimethylacatate, Prednisone, Prednival, Prednylidene, Prednylident 21-Diethlaminoacatate, Tixocoratal, Triamcinolone, Triamcinolone Acetonide, Triamcinolone Benetonide, Triamcinolone Hexacetonide GONAD-STIMULATING 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 Hexadimethrine Protamines. HEAPATOPROTECTANT such as Betaine, cltolone, Malotilate, Orazamide, Phosphorylcholine, Protoporphyrin IX, silymarin-Group, Thiotic Acid IMMUNOMODULATOR such as Amiprilose, Bucillamine, Ditiocarb Sodium, Inosine Pranobex, Muroctasin, Platonin, Procodazole, Tetramisole, 6-ary 1-5-6-dihydroimidazol-(2,1-B) Thiazole Dirivatives, Thymomodulin, Thymopentin. IMMUNOSUPPRESSANT such as Cyclophilin, Cyclosporins, FK-506, Mizoribine, Rapamycin, Rapamycin Sulfamates IONEXCHANGE RESIN such as Caracrylic Resins, Resodec, Sodium Polystyren Sulfonate LACTATION STIMULATING HORMONE such as Prolactin LH-RH AGONIST such as Buserelin, Goserelin, Leuprolide, Nafarelin, Triptorelin. LIPOTROPIC such as N-Acetylmethionine, Choline Chloride, Choline Dehydrocholate, Choline Dihydrogen Citrate, Insitol, Lecithin, Methionine LUPUS ERYTHEMATOSUS SUPPRESSANT such as Bismuth Sodium Triglycollamate, Bismuth Subsalicylate. MINERALOCORTICOID such as Aldosterone, Deoxycorticosterone, Fludrocortisone. MIOTIC such as Pilocarpus MONOAMINE OXIDASE INHIBITOR such as Phenoxypropazine, Pivalylbenzhydrazine MUCOLYTIC such as Acetylcysteine, Bromhexine, Carbocysteine, Domiodol, Letosteine, Mecysteine, Mesna, Sobrerol, Stepronin, Tiopronin, Tyloxapol MUSCLE RELAXANT (SKELETAL) such as Afloqualone, Alcuronium, Atracurium Besylate, Baclofen, Benzoquinonium, C-Calebassine, Carisoprodol, Chlorphenesin Carbamate, Chlozoxazone, Curare, Cyclobenzaprine, dantrolene, Decamethonium, Eperisone, Fazadinium, Flumetramide, Gallamine, Triethiodide, Hexacarbacholine, Hexafluorenium, Idrocilamide, Lauexium Methyl Sulfate, Leptodactyline, Memantine, Mephenesin, Metaxalone, Methocarbamol, Metocurine Iodide, Pancuronium, Pipecuriym, Promoxilane, Quinine Sulfate, Styramate, Succinylcholine, Succinylcholine Suxethonium Bromide, Tetrazepam, Thiocolchicoside, Tizanidine, Tolperisone, Tubocurarine, Vecuronium, Zoxolamine. 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, Propentofylline Pyritinol. OPHTHALMIC AGENT such as 15-ketoprostaglandins. OVARIAN HORMONE such as Relaxin OXYTOCIC such as Carboprost, Cargutocin, deaminoxytocin, Erogonovine, Gemeprost, Methylergonovine, Oxytocin, Pituitary (Posterior), Prostaglandin E2, Prostagandin F2a, Sparteine. PEPSIN INIBITOR such as Sodium Amylosulfate PERISTALTIC STIMULANT such as Cisapride PROGESTOGEN such as Allylestrenol, Anagestone, Chlormadinone Acetate, delmadinone Acetate, Demegestone, Desogestrel, Dimethisterone, Dydrogesterone, Ethinylestrenol, Ethjsterone, 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, Norvinisterone, Pentagestrone, Progesterone, Promegestone, Quingestrone, Trengestone PROLACTIN INHIBITOR such as Metegoline PROSTAGLANDIN/PROSTAGLANDIN ANALOG such as Bmeprost, Prostacyclin, Prostaglandin E1, Sulprostone PROTEASE INHIBITOR such as Aprotinin, Camostat, Ganexate, Nagamostat RESPIRATORY STIMULANT such as Almitrine, dimefine, Dimorpholamine, Doxapram, Lobeline, Mepixanox, Pimecione, Sodium Succinate, Tacrine SCLEROSING AGENT such as Ethanolamine, Ethylamine, 2-Hexyldecanoic Acid, Sodium Ricinoleate, Sodium Tetradecyl Sulgate, Tribenoside SEDATIVE/HYPNOTIC Acyclic Ureides such as Acecarnromal, Apronalide, Bomisovalum, Capuride, Carbromal, ectylurea Alcohols such as Chlorhexadol, Ethchlorvynol, 4-Methyl-5-thiazolecthanol, tert-Pentyl Alcohol, 2,2,2-Trichloroethanol Amides Such as Butoctamide, Diethylboromoacetamide, Ibrotamide, Isovaleryl Diethylamide, Niaprazine, Tricetamide, Trimerozine, Zolpidem, Zopiclone Barbituric Acid Derivatives such as Allobarbital, Amobarbital, Aprobarbital, Barbital, Brailabarbital, Butabarbital Sodium, Butalbital, Burallylonal, Butethal, Carbubarb, Cyclobarbital, Cyclopentobarbital, Enallylpropymal, 5-Ethyl-5-(piperidyl) barbituric Acid, 5-Furfuryl-5-isopropylbarbituric Acid, Heptabarbital, Hexethal Sodium, Hexobarbital, Mephobarbital, Methitural, Narocobarbital, Nealbarbital, Prntobarbital 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, Haloxazolam, Loprazolam, Lormetazepam, Nitrazepam, Quazepam, Temasepam, Triazolam Bromides such as Ammonium Bromide, Calcium Bromide, calcium Bromilactobionate, Lithium Bromide, Magnesium Bromide, Potassium Bromide, Sodium Bromide Carbamates such as Amyl Carbamate(Tertiary), Ethinamate, Hexaprpymate, Meparfynol Carbamate, Novonal, Tricholorourethan Chloral Derivatives such as Carbocloral, Chloral Betaine, Chloral Formamide, Chlotal Hydrate, Chloralantipyrine, Dichloralphenazone, Pentaerythritol Chloral, Triclofos Piperidinediones such as Glutehimide, Methyprylon, Piperione, Pyrithyldione, Taglutimide, Thalidomide Quinazolone Derivatives such as Etaqualone, Mecloqualone, Methaqualone Others such as Acetal, Acetophenone, Aldol, Ammonium Valerate, Amphenidone, d-Bornyl a-Bromoisovalerate, d-Bornyl Isovaletate, Bromoform, Calcium 2-Ethylbutanoate, Carfinate, a-Chlorolose, Clomethiazole, Cypripedium, doxylamine, Etodroxizine, Etomidate, Feradiazole, Homofenazine, Hydrobromic Acid, Mecloxamine, Menthyl Valerate, Opium, Paraldehyde, Perlapine, Propiomazine, Rilmazafone, Sodium Oxybate, Sulfonethylmethane, Sulfonmethane THROMBOLYTIC such as APSAC, Plasmin, Pro-Urokinase, Streptokinass, Tissue Plasminogen Activator, Urokinass THYROTROPIC HORMONE such as TRH, TSH MISCELLANEOUS - Vitamins, Mineral 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 Miconutrinets and their combinations with Vitamins, Antiosidants i.e. Betavarotene 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 trimellitae, cellulose carboxymethyl ethers and their salts, hydroxyproplmethyl cellulose phthalate, hydropropylmethyl cellulose acetate succinate, polyethylene, polyvinyl acetate (homopolymer), polyvinyl acetate phthalate, propylene glycolalginate, Polyvinylmethacrylate/maleic anhydride (PVM/MA) copolymer, Polyvinylpyrollidone (PVP) /dimethiconlacrylate /polycarbamyl /polyglycolester, PVP/ dimethylaminoethylmethacrylate / polycarbamyl polyglycol ester, PVP/ polycarbamyl polyglycol ester, Polyvinylpyrollidone/vinyl acetate (PVP/VA) copolymer, gelatin and Gelatin derivatives. Alginates, Carbomers, Polycarbophils. Methacrylic acid copolymers. Carrageenans, pectins, chitosans, cyclodextrins, lecitins. Natural gums containg 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 bitttter 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 manufacturing process is exemplified below: Example 1. Step 1 : Preparation of non-sugar sweetener in mucoadhesive form. Aspartame 20.00 g PVM/MA Copolymer 0.40 g (GantrezAN169) Acetone 20.00 ml 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 Nimesulide (Drug/Pharmaceutical agent) 100.0 mg Mannitol 204.5 mg Aspartame of step 1 in mucoadhesive form 7.0 mg Flavour 1.5 mg Sodium Starch Glycolate 3.0 mg Magnesium Stearate 4.0 mg 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 20.00 g Carbomer (Carbopol 934P) 0.40 g Water 20.00 ml Disperse Carbopol 934P in 20 ml Water. Granulate Aspartame with it and dry at 40°C. Sift through 60 mesh sieve. Step 2: Tablet Formulation Nimesulide (Drug/Pharmaceutical agent) 100.0 mg Mannitol 204.5 mg Aspartame 3.0 mg Aspartame of step 1 in mucoadhesive form 4.0 mg Flavour 1.5 mg Sodium Starch Glycolate 3.0 mg Magnesium Stearate 4.0 mg Sift all the ingredients through 40 mesh sieve and blend. Compress into tablets at a hardness of 1 to 5 Kg. Example 3: Step 1: Taste neutralization of drug substance. Ibuprofen (Drug/Pharmaceutical agent) 95.95 g Tribehenin 4.00 g Polysorbate 80 0.05 g Water 40.00 ml Heat water to about 50°C - 60°C. Add polysorbate 80 and mix. Under stirring add Tribehenin 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 1 200.0 mg Equivalent to Ibuprofen Xylitol 204.5 mg Aspartame in mucoadhesive form 7.00 mg (from step 1 of example 2) Flavour 1.5 mg Sodium Starch Glycolate 3.0 mg Megnesium Stearate 4.0 mg Sift all the ingredients through 40 mesh sieve and blend. Compress into tablets at a hardness of 1 to 5 Kg. Example 4: % w/w Cisapride (Drug/Pharmaceutical agent) 2.50 Liquid Paraffin 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, Croscarmellose Sodium, Aspartame (in mucoadhesive form) and Flavours through mesh no. 30 (BSS) sieve and mix with the above said bulk. Compress into tablets using conventional tabletting machine at a hardness of 1 - 3 Kg. Example 5: % w/w Cetirizine Dihydrochloride (Drug/Pharmaceutical agent) 2.5 Crosslinked Polyacrylic Acid (Ion-exchange resin) 10.0 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 dihydrochloride 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. 30 BSS) 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 - 3 Kg. Example 6: Step 1. Preparation of non-sugar sweetener in Mucoadhesive form: Saccharin Sodium 100.00 g Polycarbophil (Noveon AA-1) 4.00 g Water 10.00g 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 Crosscarmellose sodium 0.25 Povidone 0.25 Saccharin sodium in mucoadhesive form 6.25 (from step 1 of example 6) 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 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. 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 - 3 Kg. Example 7: Step 1: Taste neutralization of drug substance. Ascorbic Acid 96.00 g Gelatin 4.00 g Water 30.00 ml Heat water to about 60°C - 70°C. Add Gelatin and dissolve. Coat the Ascorbic Acid by spraying the gelatin solution using fluidized bed coater. Size the coated drug powder through 40 mesh sieve. Step 2: Mucoadhesive Sweetener. Ammonium Glycirrhizinate 20.00 g PVM/MA Copolymer 0.40 g (GantrezAN 169) Acetone 20.00 ml 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 100.0 mg Sorbitol 204.5 mg Ammonium Glycirrhizinate in Mucoadhesive form 7.00 mg (from step 2) Flavour 1.5mg Sodium Starch Glycolate 3.0 mg Megnesium Stearate 4.0 mg 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) equivalent to 18 Million I.U. Mannitol 204.5 mg Aspartame in mucoadhesive form 7.0 mg (from step 1 of example 1) Flavour 1.5mg Sodium Starch Glycolate 3.0 mg Magnesium Stearate 4.0 mg 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 98.9 mg Aspartame 0.03 mg Acesulfam 0.03 mg Neophesperidine DC in mucoadhesive form 0.04 mg 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 unpleasant of bitter taste of the drug is masked without significantly interfering with 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. We claim: 1. A novel fast dissolving pharmaceutical composition in solid dosage form with prolonged sweet taste which comprises: (a) at least one pharmaceutical active agent in an amount of from 0.1 to 99 weight % of the total dosage form; (b) at least one water soluble sugar in an amount of from 5 to 95 weight % of the total dosage form, (c) at least one non-sugar sweetener in a fast release form in an amount of from greater than 0 to 10 weight % of the total dosage form; and (d) at least one non-sugar sweetener in a mucoadhesive slow release form in an amount of from 0.5 to 20 weight % of the total dosage form. 2. A composition as claimed in claim 1, wherein the water soluble sugar is mannitol, sorbitol and/or xylitol. 3. A composition as claimed in claim 1, wherein the non-sugar sweetner is isomalt; aspartame, acesulfame potassium, saccharine sodium, cyclamates, neohesperidine and/or glycirrhizin. 4. A process for the preparation of a fast dissolving pharmaceutical composition in solid dosage form with prolonged sweet taste as claimed in claim 1, which comprises mixing the following ingredients:- a. at least one drug/pharmaceutically active agent in an amount of from 0.1 to 99 weight % of the total dosage form; b. at least one water soluble sugar in an amount of from 5 to 95 weight % of the total dosage form; c. at least one non-sugar sweetener in fast release form in an amount of from greater than 0 to 10 weight % of the total dosage form; and d. at least one non-sugar sweetener in a mucoadhesive slow release form in an amount of from 0.5 to 20 weight % of the total dosage form; and compressing the resulting mixture into a 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, wherein the non-sugar sweetner is isomalt, aspartame, acesulfame potassium, saccharine sodium, cyclamates, neohesperidine and/or glycirrhizin. 7. A novel fast dissolving pharmaceutical composition in solid dosage form with prolonged sweet taste substantially as here described in refere to the foregoing description and examples. 8. A process for the preparation of a fast dissolving pharmaceutical composition in solid dosage form with prolonged sweet taste substantially as here described in refere to the foregoing description and examples. |
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1514-del-1999-correspondence-others.pdf
1514-del-1999-correspondence-po.pdf
1514-del-1999-description (complete).pdf
1514-del-1999-petition-137.pdf
1514-del-1999-petition-138.pdf
Patent Number | 255203 | |||||||||
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Indian Patent Application Number | 1514/DEL/1999 | |||||||||
PG Journal Number | 06/2013 | |||||||||
Publication Date | 08-Feb-2013 | |||||||||
Grant Date | 02-Feb-2013 | |||||||||
Date of Filing | 30-Nov-1999 | |||||||||
Name of Patentee | PANACEA BIOTEC LIMITED | |||||||||
Applicant Address | B-1 EXTN./A-27 MOHAN CO-OPERATIVE INDUSTRIAL ESTATE, MATHURA ROAD, NEW DELHI 10044-INDIA | |||||||||
Inventors:
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PCT International Classification Number | A61K 9/28 | |||||||||
PCT International Application Number | N/A | |||||||||
PCT International Filing date | ||||||||||
PCT Conventions:
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