NOVEL TABLET DOSAGE FORM

• US 20100196471A1
• Filed: 03/25/2008
• Published: 08/05/2010
• Est. Priority Date: 05/30/2007
• Status: Active Grant

• Current Assignee: Girish Kumar Jain, Rahul Dabre, Ramakant Gundu
• Original Assignee: Girish Kumar Jain, Rahul Dabre, Ramakant Gundu
• Inventors: Gundu, Ramakant, Jain, Girish Kumar, Dabre, Rahul
• Granted Patent: US 8,574,625 B2
• Time in Patent Office: Days
• US Class Current: 424/465
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/196 the amino group being directly attached to a ring, e.g. anthranilic acid, mefenamic acid, diclofenac, chlorambucil
• CPC Class Codes: A61K 31/40 having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
• CPC Class Codes: A61K 31/4184 condensed with carbocyclic rings, e.g. benzimidazoles
• CPC Class Codes: A61K 31/4418 having a carbocyclic group directly attached to the heterocyclic ring, e.g. cyproheptadine
• CPC Class Codes: A61K 31/4422 1,4-Dihydropyridines, e.g. nifedipine, nicardipine
• CPC Class Codes: A61K 31/55 having seven-membered rings, e.g. azelastine, pentylenetetrazole
• CPC Class Codes: A61K 31/557 Eicosanoids, e.g. leukotrienes or prostaglandins
• CPC Class Codes: A61K 31/5575 having a cyclopentane, e.g. prostaglandin E2, prostaglandin F2-alpha
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61K 9/2072 characterised by shape, structure or size; Tablets with holes, special break lines or identification marks; Partially coated tablets; Disintegrating flat shaped forms A61K9/0004, A61K9/0056, A61K9/0065 take precedence
• CPC Class Codes: A61K 9/209 containing drug in at least two layers or in the core and in at least one outer layer
• CPC Class Codes: A61K 9/2886 having two or more different drug-free coatings; Tablets of the type inert core-drug layer-inactive layer of the type active core-drug layer-inactive layer A61K9/209
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 31/00 Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system

Abstract

The present invention relates to novel tablet dosage forms and methods of preparing these forms, which can be used for different classes of pharmaceutical active ingredients posing stability issues in a single unit system. The dosage form includes a first layer, which includes a tablet of one or more active pharmaceutical ingredients, which is inlayed in the first layer along with other pharmaceutically acceptable excipients, and a second layer that includes one or more active pharmaceutical ingredients optionally with other pharmaceutically acceptable excipients.

Claims

1. A tablet dosage form comprising:

a) a first layer comprising a tablet of one or more active pharmaceutical ingredients, wherein the tablet is inlayed in the first layer with one or more other pharmaceutically acceptable excipients; and

b) a second layer comprising or more active pharmaceutical ingredients and optionally other pharmaceutically acceptable excipients.

2. The dosage form of claim 1, wherein the one or more active pharmaceutical ingredients is present in an immediate release, delayed release, sustained release, extended release, controlled release or modified release form.

3. The dosage form of claim 1, wherein the dosage form comprises a bilayered dosage form.

4. The dosage form of claim 1, further comprising coating the tablet with one or more enteric polymers, pharmaceutically acceptable seal coat polymers or rate controlling polymers.

5. The dosage form of claim 4, wherein the enteric polymer comprises one or more of methacrylic acid/methyl methacrylate copolymers, cellulose acetate phthalate, hydroxypropylmethyl cellulose phthalate, hydroxypropylmethyl cellulose acetate succinate, polyvinyl acetate phthalate, and cellulose acetate trimellitate.

6. The dosage form of claim 4, wherein the pharmaceutically acceptable seal coat polymer comprises one or more of hydroxypropyl methylcellulose, hydroxypropyl cellulose and cellulose ethers.

7. The dosage form of claim 4, wherein the rate-controlling polymer comprises one or more of hydrophilic and hydrophobic polymers.

8. The dosage form of claim 7, wherein the rate controlling polymer comprises one or more of polyvinyl acetate, cellulose acetate, cellulose acetate butyrate, cellulose acetate propionate, ethyl cellulose, a fatty acid, a fatty acid ester, an alkyl alcohol, a wax, shellac, rosin, zein (prolamine from corn), a poly(meth)acrylate, microcrystalline cellulose or poly(ethylene oxide), polyuronic acid salts, cellulose ethers, xanthan gum, tragacanth gum, gum karaya, guar gum, acacia, gellan gum locust bean gum, alkali metal salts of alginic acid or pectic acid, sodium alginate, potassium alginate, ammonium alginate, hydroxypropyl cellulose, hydroxypropyl methylcellulose, and carboxyvinyl polymers.

9. The dosage form of claim 1, wherein the one or more active pharmaceutical ingredients comprise one or more of anti-inflammatory agents, sedatives, hypnotics, antibiotics, antidiabetics, antihypertensives, anti-osteoporosis agents, antithrombotic agents, antivirals, antifungals, anticholinergic agents, anxiolytic agents, adrenergics, antipsychotics, anti-parkinsonism agents, anticonvulsants, antiepileptics, CNS stimulants, antianginal agents, antiarrhythmics, antihyperlipidemic drugs, diuretics, antiasthmatics, anticoagulants, antianemia agents, vitamins, hormones, antihistaminics, anticancer agents, antiallergics, antiarthritis agents, antialzheimers'"'"' agents, vasopressin antagonists, anticonvulsants, steroids, anesthetics, thrombolytics, antacids, proton pump inhibitors, protease inhibitors, platelet aggregation inhibitors, mucolytics, antimalarials, antiemetics, laxatives, expectorants, enzymes, contraceptives, bronchodilators, antitussives, antimigraine agents, anthelmintics, and anorexiants.

10. The dosage form of claim 9, wherein the one or more active pharmaceutical ingredients comprise one or more of amlodipine, diazepam, paracetamol, aspirin, ciprofloxacin, dicyclomine, celecoxib, alendronate, diacerein, acyclovir, fluconazole, epinephrine, divalproex, methylphenidate, flecainide, metoprolol, fenofibrate, hydrochlorothiazide, montelukast, heparin, warfarin, hemoglobin, iron, ascorbic acid, leutinizing hormone, bicalutamide, donepezil, tolvaptan, cortisones, lidocaine, calcium carbonate, saquinavir, bromhexine, promethazine, bisacodyl, pancreatin, ethinyl estradiol, salbutamol, diphenhydramine, sumatriptan, diclofenac, metronidazole, orlistat, ibuprofen, indomethacin, ketorolac, tramadolol, oxcarbazepine, pioglitazone, rosiglitazone, miglitol, vildagliptin, sitagliptin, repaglinide, voglibose, alprazolam, chlorpromazine, cimetidine, pseudoephedrine, naproxen, piroxicam, atenolol, benazepril, captopril, lisinopril, fosinopril, enalapril, furosemide, indapamide, atenolol, felodipine, verapamil, cartenolol, carvedilol, cerivastatin, diltiazem, fluvastatin, irbesartan, candesartan, methyldopa, reserpine, bupropion, fluoxetine, paroxetine, escitalopram, sertraline, amitryptiline, imipramine, fexofenadine, clopidogrel, entacapone, levodopa, carbidopa, levetiracetam, venlafaxine, duloxetine, lisinopril, losartan, lovastatin, niacin, pravastatin, ramipril, simvastatin, atorvastatin, valsartan, telmisartan, sildenafil, tadalafil, vardenafil, esomeprazole, famotidine, omeprazole, pantoprazole, rabeprazole, ranitidine, simethicone, artesunate, amodiaquine, benazepril, misoprostol, metformin, glipizide, and their pharmaceutically acceptable salts.

11. The dosage form of claim 1, wherein the one or more active pharmaceutical ingredients comprise one or both of diclofenac and misoprostol or their pharmaceutically acceptable salts.

12. The dosage form of claim 1, wherein the pharmaceutically acceptable excipients comprise one or more of binders, fillers, antioxidants, disintegrants, surfactants, lubricants and glidants.

13. A tablet dosage form comprising:

a) a first layer comprising a tablet of diclofenac or a salt thereof, wherein the tablet is inlayed in the first layer with other pharmaceutically acceptable excipients; and

b) a second layer comprising misoprostol or a salt thereof and optionally other pharmaceutically acceptable excipients.

14. The dosage form of claim 13, further comprising coating the tablet with one or more enteric polymers or pharmaceutically acceptable seal coat polymers.

15. The dosage form of claim 14, wherein the enteric polymer comprises one or more of methacrylic acid/methyl methacrylate copolymers, cellulose acetate phthalate, hydroxypropylmethyl cellulose phthalate, hydroxypropylmethyl cellulose acetate succinate, polyvinyl acetate phthalate, and cellulose acetate trimellitate.

16. The dosage form of claim 14, wherein the pharmaceutically acceptable seal coat polymer comprises one or more of hydroxypropyl methylcellulose, hydroxypropyl cellulose and cellulose ethers.

17. The dosage form of claim 13, wherein the dosage form exhibits a dissolution profile such that within first 2 hours less than 2% of diclofenac or a salt thereof is released, when the release rate is measured in Apparatus 2 (USP, Dissolution, paddle, 50 rpm) using 900 ml of 0.1N HCl at 37°

C.±

0.5°

C. and within first 30 minutes more than 75% of diclofenac or a salt thereof is released, when the release rate is measured in Apparatus 2 (USP, Dissolution, paddle, 50 rpm) using 900 ml of pH 6.8 phosphate buffer at 37°

C.±

0.5°

C.

18. The dosage form of claim 13, wherein the pharmaceutically acceptable excipients comprise one or more of binders, fillers, antioxidants, solubilizing agents, disintegrants, surfactants, lubricants and glidants.

19. The dosage form of claim 13, wherein the dosage form comprises a bilayered dosage form.

20. A process of preparing pharmaceutical composition, which process comprises of compressing

a) first layer comprising of tablets of one or more active pharmaceutical ingredients with inert pharmaceutically acceptable excipients;

and

b) the second layer comprising of one or more active pharmaceutical ingredients along with inert pharmaceutically acceptable excipients into tablet dosage form.

21. The process of claim 20, wherein the one or more active pharmaceutical ingredients is present in an immediate release, delayed release, sustained release, extended release, controlled release or modified release form.

22. The process of claim 20, wherein the dosage form comprises a bilayered dosage form.

23. The process of claim 20, further comprising coating the tablet with one or more enteric polymers, pharmaceutically acceptable seal coat polymers or rate controlling polymers.

24. The process of claim 23, wherein the enteric polymer comprises one or more of methacrylic acid/methyl methacrylate copolymers, cellulose acetate phthalate, hydroxypropylmethyl cellulose phthalate, hydroxypropylmethyl cellulose acetate succinate, polyvinyl acetate phthalate, and cellulose acetate trimellitate.

25. The process of claim 23, wherein the pharmaceutically acceptable seal coat polymer comprises one or more of hydroxypropyl methylcellulose, hydroxypropyl cellulose and cellulose ethers.

26. The process of claim 23, wherein the rate-controlling polymer comprises one or more of hydrophilic and hydrophobic polymers.

27. The process of claim 26, wherein the rate controlling polymer comprises one or more of polyvinyl acetate, cellulose acetate, cellulose acetate butyrate, cellulose acetate propionate, ethyl cellulose, a fatty acid, a fatty acid ester, an alkyl alcohol, a wax, shellac, rosin, zein (prolamine from corn), a poly(meth)acrylate, microcrystalline cellulose or poly(ethylene oxide), polyuronic acid salts, cellulose ethers, xanthan gum, tragacanth gum, gum karaya, guar gum, acacia, gellan gum locust bean gum, alkali metal salts of alginic acid or pectic acid, sodium alginate, potassium alginate, ammonium alginate, hydroxypropyl cellulose, hydroxypropyl methylcellulose, and carboxyvinyl polymers.

28. The process of claim 20, wherein the one or more active pharmaceutical ingredients comprise one or more of anti-inflammatory agents, sedatives, hypnotics, antibiotics, antidiabetics, antihypertensives, anti-osteoporosis agents, antithrombotic agents, antivirals, antifungals, anticholinergic agents, anxiolytic agents, adrenergics, antipsychotics, anti-parkinsonism agents, anticonvulsants, antiepileptics, CNS stimulants, antianginal agents, antiarrhythmics, antihyperlipidemic drugs, diuretics, antiasthmatics, anticoagulants, antianemia agents, vitamins, hormones, antihistaminics, anticancer agents, antiallergics, antiarthritis agents, antialzheimers'"'"' agents, vasopressin antagonists, anticonvulsants, steroids, anesthetics, thrombolytics, antacids, proton pump inhibitors, protease inhibitors, platelet aggregation inhibitors, mucolytics, antimalarials, antiemetics, laxatives, expectorants, enzymes, contraceptives, bronchodilators, antitussives, antimigraine agents, anthelmintics, and anorexiants.

29. The process of claim 28, wherein the one or more active pharmaceutical ingredients comprise one or more of amlodipine, diazepam, paracetamol, aspirin, ciprofloxacin, dicyclomine, celecoxib, alendronate, diacerein, acyclovir, fluconazole, epinephrine, divalproex, methylphenidate, flecainide, metoprolol, fenofibrate, hydrochlorothiazide, montelukast, heparin, warfarin, hemoglobin, iron, ascorbic acid, leutinizing hormone, bicalutamide, donepezil, tolvaptan, cortisones, lidocaine, calcium carbonate, saquinavir, bromhexine, promethazine, bisacodyl, pancreatin, ethinyl estradiol, salbutamol, diphenhydramine, sumatriptan, diclofenac, metronidazole, orlistat, ibuprofen, indomethacin, ketorolac, tramadolol, oxcarbazepine, pioglitazone, rosiglitazone, miglitol, vildagliptin, sitagliptin, repaglinide, voglibose, alprazolam, chlorpromazine, cimetidine, pseudoephedrine, naproxen, piroxicam, atenolol, benazepril, captopril, lisinopril, fosinopril, enalapril, furosemide, indapamide, atenolol, felodipine, verapamil, cartenolol, carvedilol, cerivastatin, diltiazem, fluvastatin, irbesartan, candesartan, methyldopa, reserpine, bupropion, fluoxetine, paroxetine, escitalopram, sertraline, amitryptiline, imipramine, fexofenadine, clopidogrel, entacapone, levodopa, carbidopa, levetiracetam, venlafaxine, duloxetine, lisinopril, losartan, lovastatin, niacin, pravastatin, ramipril, simvastatin, atorvastatin, valsartan, telmisartan, sildenafil, tadalafil, vardenafil, esomeprazole, famotidine, omeprazole, pantoprazole, rabeprazole, ranitidine, simethicone, artesunate, amodiaquine, benazepril, misoprostol, metformin, glipizide, and their pharmaceutically acceptable salts.

30. The process of claim 20, wherein the one or more active pharmaceutical ingredients comprise one or both of diclofenac and misoprostol or their pharmaceutically acceptable salts.