Drug – bio-affecting and body treating compositions – Preparations characterized by special physical form – Capsules
Patent
1996-03-22
1998-03-24
Page, Thurman K.
Drug, bio-affecting and body treating compositions
Preparations characterized by special physical form
Capsules
424465, 424434, 424476, 424489, 424456, 424453, 424457, A61K 948
Patent
active
057310009
DESCRIPTION:
BRIEF SUMMARY
The present invention relates to pharmaceutical compositions comprising bupropion hydrochloride and a pharmaceutically acceptable stabiliser and methods of stabilising bupropion hydrochloride in a pharmaceutical composition.
Bupropion hydrochloride is a known antidepressant sold in instant release tablet form under the brand name WELLBUTKIN.RTM.. (Also see U.S. Pat. Nos. 3,819,706 and 3,885,046; 1993 Physicians Desk Reference and the Merck Index, Eleventh Edition, Entry No. 1488. Bupropion hydrochloride is also useful as an anticholesterol agent, in suppressing prolactin secretion, in preventing functional impairment and drowsiness seen upon administration of benzodiazepine, in the treatment of minimal brain dysfunction, tardive dyskinesia, impaired mental alertness upon ingestion of ethanol and psychosexual dysfunction. While the instant release tablets currently sold are quite suitable for the indicated use, the method of manufacturing these is less than desirable based on cost as well as process conditions.
The object of the present invention is to prevent (inhibit) the degradation of bupropion hydrochloride, using stabiliser ingredients, thus allowing the preparation of pharmaceutical compositions such as instant and sustained release tablets and capsules which, from a cost of manufacture and processing standpoint, are much improved over those achievable in the past.
Thus the present invention provides a pharmaceutical composition in solid form comprising bupropion hydrochloride and a pharmaceutically acceptable stabiliser in an effective stabilising amount, 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.
Alternatively, the present invention also provides 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.
The preferred pH of the aqueous solution of the stabiliser is 0.9 to about 2 and most preferably 1.
Preferably the pharmaceutical composition according to the present invention contains at least about 90% w/w of undegraded bupropion hydrochloride after storage for 6 weeks under the above conditions and more preferably 95% or even 98%. In an additional aspect, the amount of undegraded bupropion hydrochloride is greater than 80% of its labelled strength, and more preferably greater than 90% percent of the labelled strength after one year of storage under the humidity and temperature conditions usually encountered in pharmacies and medicine cabinets i.e. room temperature and 35-60% humidity. Thus, when used in a pharmaceutical preparation for example, a tablet will still retain at least 80% of its potency and preferably at least 90% after one year of storage at room temperature (15.degree.-25.degree. C. (59.degree.-77.degree. F.)) at 35-60% humidity. For example if the tablet initially contains 100 mg bupropion hydrochloride (labelled amount) at time of preparation, after one year storage at least 80 mg of undegraded bupropion hydrochloride will remain in the tablet.
The amount of the stabiliser which may be used with the present invention may vary but preferably is about 2.7% to 27%, most preferably about 5% to 16.2% based on the label strength of bupropion hydrochloride in the ph
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Kalidindi Sanyasi Raju
Ruff Michael David
Sutton, Jr. Joel Elmore
Benston, Jr. William E.
Glaxo Wellcome Inc.
Makujina Shah R.
Page Thurman K.
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