PHARMACEUTICAL COMPOSITIONS FOR REDUCING ALCOHOL-INDUCED DOSE DUMPING

• US 20120207825A1
• Filed: 09/09/2010
• Published: 08/16/2012
• Est. Priority Date: 09/17/2009
• Status: Abandoned Application

• Current Assignee: Cadila Healthcare Limited (Zydus Lifesciences Limited)
• Original Assignee: Cadila Healthcare Limited (Zydus Lifesciences Limited)
• Inventors: Roy, Sunilendu Bhushan, Kulkarni, Sushrut Krishnaji, Panchal, Maulik Kiritkumar, Shah, Kartik Yogeshkumar
• Application Number:
  US13/393,658
• Publication Number:
  US 20120207825A1
• Time in Patent Office: Days
• US Class Current: 424/452
• CPC Class Codes: A61K 9/2866 Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
• 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: A61K 9/5042 Cellulose; Cellulose derivatives, e.g. phthalate or acetate succinate esters of hydroxypropyl methylcellulose
• CPC Class Codes: A61K 9/5047 Cellulose ethers containing no ester groups, e.g. hydroxypropyl methylcellulose
• CPC Class Codes: A61K 9/5078 with drug-free core
• CPC Class Codes: A61P 19/10 for osteoporosis
• CPC Class Codes: A61P 25/20 Hypnotics; Sedatives
• CPC Class Codes: A61P 25/22 Anxiolytics
• 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 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 31/00 Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
• CPC Class Codes: A61P 31/10 Antimycotics
• CPC Class Codes: A61P 31/12 Antivirals
• CPC Class Codes: A61P 7/02 Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
• CPC Class Codes: A61P 9/12 Antihypertensives

Abstract

A pharmaceutical composition is disclosed. The composition comprises a core comprising an active substance or a salt thereof; a separating layer comprising at least one sugar; and a functional layer comprising at least one pharmaceutically acceptable polymer, wherein the composition is resistant to dose dumping in presence of alcohol.

Claims

1. A pharmaceutical composition comprising a core comprising an active substance or a salt thereof;

a separating layer comprising at least one sugar; and

a functional layer comprising at least one pharmaceutically acceptable polymer, wherein the composition is resistant to dose dumping in presence of alcohol.

2. The composition as claimed in claim 1, wherein the separating layer further comprises a binder and an anti-tacking agent.

3. The composition as claimed in claim 1, wherein the sugar comprises one or more of sucrose, lactose, dextrin, dextrose, fructose, glucose, mannitol, sorbitol, trehalose, xylitol, isomalt, maltitol, inositol, and lactitol.

4. The composition as claimed in claim 1, wherein the sugar is sucrose.

5. The composition as claimed in claim 1, wherein the sugar is lactose.

6. The composition as claimed in claim 2, wherein the binder comprises one or more of hydroxyethyl cellulose, hydroxypropyl cellulose, hydroxypropyl methylcellulose, carbomers, dextrin, ethyl cellulose, methylcellulose, shellac, zein, gelatin, polymethacrylates, polyvinyl pyrrolidone, pregelatinized starch, sodium alginate, gums, and synthetic resins.

7. The composition as claimed in claim 2, wherein the binder is hydroxypropyl methylcellulose.

8. The composition as claimed in claim 2, wherein the anti-tacking agent comprises one or more of talc, magnesium stearate, calcium stearate, zinc stearate, colloidal silicon dioxide, finely divided silicon dioxide, stearic acid, hydrogenated vegetable oil, glyceryl palmitostearate, glyceryl monostearate, glyceryl behenate, polyethylene glycols, powdered cellulose, starch, sodium stearyl fumarate, sodium benzoate, mineral oil, magnesium trisilicate, and kaolin.

9. The composition as claimed in claim 2, wherein the anti-tacking agent is talc.

10. The composition as claimed in claim 1, wherein the separating layer comprises a sugar and a binder in a ratio of from 1:

0.5 to 1;

2.

11. The composition as claimed in claim 1, wherein the separating layer comprises a sugar, a binder and anti-tacking agent in a ratio of from 80:

10;

10 to 20;

70;

10.

12. The composition as claimed in claim 1, wherein the polymer is a rate controlling polymer.

13. The composition as claimed in claim 12, wherein the rate controlling polymer provides sustained release, controlled release or extended release of the active substance from the composition.

14. The composition as claimed in claim 12, wherein the rate controlling polymer provides delayed release of the active substance from the composition.

15. The composition as claimed in claim 1, wherein the polymer comprises one or more of hydrophilic polymers and hydrophobic polymers.

16. The composition as claimed in claim 1, wherein the polymer comprises one or more of ethylcellulose, hydroxypropyl methylcellulose, hydroxypropyl cellulose, methylcellulose, carboxymethylcellulose, hydroxymethylcellulose, hydroxyethylcellulose, waxes, polyvinylacetate, polymethacrylates, and hydrogenated castor oil.

17. The composition as claimed in claim 1, wherein the polymer comprises one or more of cellulose acetate phthalate, cellulose acetate succinate, methylcellulose phthalate, hydroxy propyl methylcellulose phthalate, ethylhydroxycellulose phthalate, polyvinylacetate phthalate, polyvinyl butyrate acetate, vinyl acetate-maleic anhydride copolymer, styrene-maleic mono-ester copolymer, polymethacrylates such as methyl acrylate-methacrylic acid copolymer, methacrylate-methacrylic acid-octyl acrylate copolymer, and hydrogenated castor oil.

18. The composition of claim 1, wherein the active substance is selected from the therapeutic category of drugs like anti-inflammatory agents, sedatives, hypnotics, antibiotics, antidiabetics, antihypertensives, anti-osteoporosis agents, antithrombotic agents, antivirals, antifungals, anticholinergic agents, anxiolytic agents, adrenergics, antipsychotics, anti-parkinsonism agents, anti convulsants, antiepileptics, CNS stimulants, antianginal agents, antiarrhythmics, anti-hyperlipidemic drugs, diuretics, antiasthmatics, anticoagulants, antianemia agents, vitamins, hormones, antihistaminics, anticancer agents, antiallergics, antiarthritis agents, antialzheimers'"'"' agents, vasopressin antagonists, anticonvulsants, steroids, an esthetics, thrombolytics, antacids, proton pump inhibitors, protease inhibitors, platelet aggregation inhibitors, mucolytics, antimalarials, antiemetics, laxatives, expectorants, enzymes, contraceptives, bronchodilators, antitussives, antimigraine agents, anthelmintics, and anorexiants.

19. The composition of claim 1, wherein the active substance comprises one or more of venlafaxine, duloxetine, cyclobenzaprine, quetiapine, trospium, propranolol, morphine, oxycodone, oxymorphone, amlodipine, hydrocodone, diazepam, paracetamol (acetaminophen), aspirin, ciprofloxacin, dicyclomine, celecoxib, alendronate, diacerein, acyclovir, fluconazole, epinephrine, divalproex, methylphenidate, 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, 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, or their pharmaceutically acceptable salts.

20. The composition of claim 1, wherein the composition further comprises one or more pharmaceutically acceptable excipients comprising diluents, disintegrants, binders, lubricants, glidants, plasticizers, anti-tacking agents, and opacifying agents.

21. The composition of claim 1, wherein the composition is in the form of a tablet, capsule, granules, pellets, powder, sachet, minitablets, microtablets, microspheres, microcapsules, bilayer tablet, layered tablet, tablet in a tablet, or tablets in a capsule.

22. The composition of claim 1, wherein the composition is a capsule.

23. A pharmaceutical composition comprising a core comprising an active substance or a salt thereof;

a separating layer comprising at least one sugar; and

a functional layer comprising at least one pharmaceutically acceptable polymer, wherein the composition is resistant to dose dumping in presence of alcohol and wherein less than 40% of the active ingredient is released from the composition after 60 minutes in the presence of 40% alcohol at pH 1.2.

24. A process for preparing a pharmaceutical composition, the process comprising:

(i) preparing a core comprising an active substance or a salt thereof;

(ii) applying a separating layer comprising at least one sugar on the core;

(iii) applying a functional layer comprising at least one pharmaceutically acceptable polymer on the coated core of step (ii); and

(iv) converting into a suitable finished dosage form.

25. The process as claimed in claim 24, wherein the composition further comprises one or more pharmaceutically acceptable excipients comprising diluents, disintegrants, binders, lubricants, glidants, plasticizers, anti-tacking agents, and opacifying agents.