Claims for Patent: 5,731,000

Summary for Patent: 5,731,000

Title:	Stabilized pharmaceutical composition containing bupropion
Abstract:	This application discloses a method of inhibiting degradation of the antidepressant bupropion hydrochloride in a solid pharmaceutical formulation, so that the pharmaceutical formulation will maintain at least 80% of its initial bupropion potency after one year.
Inventor(s):	Ruff; Michael David (Greenville, NC), Kalidindi; Sanyasi Raju (Edison, NJ), Sutton, Jr.; Joel Elmore (Greenville, NC)
Assignee:	Glaxo Wellcome Inc. (Rtp, NC)
Application Number:	08/586,916
Patent Claims:	1. A pharmaceutical composition in solid form comprising bupropion hydrochloride and a pharmaceutically acceptable stabiliser in an effective stabilising mount, in which the composition contains at least about 80% w/w of undegraded bupropion hydrochloride after storage for 6 weeks at about 40.degree. C. and 75% relative humidity and in which an aqueous solution of the stabiliser in a concentration of about 6% w/w has a pH of about 0.9 to about 4, the stabiliser being selected from an organic acid, a carboxylic acid, an acid salt of an amino acid and sodium metabisulphite. 2. A pharmaceutical composition in solid form comprising bupropion hydrochloride and a pharmaceutically acceptable stabiliser in an effective stabilising mount, in which the composition contains at least about 80% w/w of undegraded bupropion hydrochloride after storage for 6 weeks at about 50.degree. C. and 27% relative humidity and in which an aqueous solution of the stabiliser in a concentration of about 6% w/w has a pH of about 0.9 to about 4, the stabiliser being selected from an organic acid, a carboxylic acid other than ascorbic acid and isoascorbic acid, an acid salt of an amino acid and sodium metabisulphite. 3. A pharmaceutical composition according to claim 1, wherein the aqueous solution of the stabiliser has a pH of about 0.9 to 2. 4. A pharmaceutical composition according to claim 1, wherein the aqueous solution of the stabiliser has a pH of around 1. 5. A pharmaceutical composition according to claim 1 which contains at least 95% w/w of undegraded bupropion hydrochloride. 6. A pharmaceutical composition according to claim 1, wherein the amount of stabiliser is 2.7% to 27% of the weight of bupropion hydrochloride in the composition. 7. A pharmaceutical composition according to claim 2, wherein the amount of stabiliser is 5% to 16.2% of the weight of bupropion hydrochloride in the composition. 8. A pharmaceutical composition according to claim 1, wherein the acid salt of the amino acid is cysteine hydrochloride, glycine hydrochloride or cystine dihydrochloride. 9. A pharmaceutical composition according to claim 1, wherein the organic acid is tartaric acid, citric acid or malic acid. 10. A pharmaceutical composition according to claim 1 wherein the carboxylic acid is ascorbic acid or isoascorbic acid. 11. A tablet or capsule according to claim 1, wherein the mount of bupropion hydrochloride is 50, 75, 100 or 150 mg. 12. A method of stabilising bupropion hydrochloride in a solid pharmaceutical composition so that at least about 80% w/w of bupropion hydrochloride is present in the undegraded form after storage for 6 weeks at about 40.degree. C. and 75% relative humidity, wherein said method comprises mixing bupropion hydrochloride with a stabiliser of which an aqueous solution in a concentration of about 6% w/w has a pH of about 0.9 to about 4, the stabiliser being selected from an organic acid, a carboxylic acid, an acid salt of an amino acid and sodium metabisulfite. 13. A method of stabilising bupropion hydrochloride in a solid pharmaceutical composition so that at least about 80% w/w of bupropion hydrochloride is present in the undegraded from after storage for 6 weeks at about 50.degree. C. and 27% relative humidity, wherein said method comprises mixing bupropion hydrochloride with a stabiliser of which an aqueous solution in a concentration of about 6% w/w has a pH of about 0.9 to about 4, the stabiliser being selected from an organic acid, a carboxylic acid other than ascrobic acid or isoascrobic acid, an acid salt of an amino acid and sodium metabisulfite. 14. A pharmaceutical composition according to claim 2, wherein the aqueous solution of the stabiliser has a pH of about 0.9 to 2. 15. A pharmaceutical composition according to claim 2, wherein the aqueous solution of the stabiliser has a pH of around 1. 16. A pharmaceutical composition according to claim 2 which contains at least 95% w/w of undegraded bupropion hydrochloride. 17. A pharmaceutical composition according to claim 2, wherein the acid salt of the acid is cysteine hydrochloride, glycine hydrochloride or cystine dihydrochloride. 18. A pharmaceutical composition according to claim 2, wherein the organic acid is tartaric acid, citric acid or malic acid. 19. A pharmaceutical composition according to claim 2 wherein the carboxylic acid is ascorbic acid or isoascorbic acid. 20. A tablet or capsule according to claim 2, wherein the amount of bupropion hydrochloride is 50, 75, 100 or 150 mg. 21. A pharmaceutical composition according to claim 1, wherein the aqueous solution of the stabiliser has a pH of about 0.9 to 2; the composition contains at least 95% w/w of undegraded bupropion hydrochloride; the amount of stabiliser is 2.7% to 27% of the weight of bupropion hydrochloride in the composition; the acid salt of the amino acid is cysteine hydrochloride, glycine hydrochloride or cystine dihydrochloride; the organic acid is tartaric acid, citric acid or malic acid; the carboxylic acid is ascorbic acid or isoascorbic acid; and wherein the amount of bupropion hydrochloride is 50, 75, 100 or 150 mg. 22. A pharmaceutical composition according to claim 2, wherein the aqueous solution of the stabiliser has a pH of about 0.9 to 2; the composition contains at least 95% w/w of undegraded bupropion hydrochloride; the amount of stabiliser is 2.7% to 27% of the weight of bupropion hydrochloride in the composition; the acid salt of the amino acid is cysteine hydrochloride, glycine hydrochloride or cystine dihydrochloride; the organic acid is tartaric acid, citric acid or malic acid; the carboxylic acid is ascorbic acid or isoascorbic acid; and wherein the amount of bupropion hydrochloride is 50, 75, 100 or 150 mg.