Modified release formulations of a bupropion salt

• US 7,241,805 B2
• Filed: 06/27/2006
• Issued: 07/10/2007
• Est. Priority Date: 06/27/2005
• Status: Active Grant

• Current Assignee: Valeant International (Barbados) Srl (Bausch Health Cos., Inc.)
• Original Assignee: Biovail Laboratories Incorporated (Bausch Health Cos., Inc.)
• Inventors: Massardo, Pietro, Zhou, Fang, Saleh, Mohammad Ashty, Maes, Paul, Oberegger, Werner, Turchetta, Stefano, Jackson, Graham
• Primary Examiner(s): Page; Thurman K.
• Assistant Examiner(s): Lao; MLouisa
• Application Number:
  US11/475,252
• Publication Number:
  US 20070027213A1
• Time in Patent Office: 378 Days
• Field of Search: 424/464
• US Class Current: 514/463
• CPC Class Codes: A61K 31/135 having aromatic rings , e.g. ketamine, nortriptyline methadone A61K31/137
• CPC Class Codes: A61K 31/137 Arylalkylamines, e.g. amphetamine, epinephrine, salbutamol, ephedrine or methadone
• CPC Class Codes: A61K 9/0004 Osmotic delivery systems; Sustained release driven by osmosis, thermal energy or gas
• CPC Class Codes: A61K 9/2027 obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
• CPC Class Codes: A61K 9/28 Dragees; Coated pills or tablets , e.g. with film or compression coating A61K9/2072 takes precedence, e.g. partially coated tablets A61K9/2072, coated multilayer tablets A61K9/2086, tablets with drug-coated core A61K9/209
• CPC Class Codes: A61K 9/2846 Poly(meth)acrylates
• 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: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/06 Antimigraine agents
• CPC Class Codes: A61P 25/18 Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
• CPC Class Codes: A61P 25/24 Antidepressants
• CPC Class Codes: A61P 25/30 for treating abuse or dependence
• CPC Class Codes: A61P 25/34 Tobacco-abuse
• 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 3/00 Drugs for disorders of the metabolism of the blood or the extracellular fluid A61P7/00
• CPC Class Codes: A61P 3/02 Nutrients, e.g. vitamins, minerals
• CPC Class Codes: A61P 3/04 Anorexiants; Antiobesity agents
• CPC Class Codes: A61P 31/12 Antivirals
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 9/10 : for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
• CPC Class Codes: C07B 2200/13 : Crystalline forms, e.g. polymorphs
• CPC Class Codes: C07C 225/16 : and containing six-membered aromatic rings

Abstract

The present invention relates to pharmaceutical compositions, formulations and medicaments comprising a bupropion salt, in particular, modified-release tablets comprising an effective amount of bupropion hydrobromide, and the use of the bupropion salt to prepare a medicament to treat a condition.

Claims

1. A modified release bupropion hydrobromide tablet suitable for oral administration having enhanced stability comprising:

(a) a core comprising (i) a therapeutically effective amount of a bupropion hydrobromide salt, (ii) a binder, and (iii) a lubricant;

(b) a controlled release polymeric coat which surrounds said core; and

(c) a 3-CBZ degradation product;

wherein said modified release bupropion hydrobromide tablet provides for the controlled release of said bupropion hydrobromide salt from said modified release bupropion hydrobromide tablet over a period of about 24 hours and has enhanced stability such that;

(1) at about 13 days after formulation of said modified release bupropion hydrobromide tablet, said modified release bupropion hydrobromide tablet contains an increase in the amount of said 3-CBZ degradation product of no more than about 0.070 expressed in percent increase of 3-CBZ degradation product relative to thc amount of 3-CBZ degradation product present in said modified release bupropion hydrobromide tablet at said tablet formulation, and

(2) at about 20 days after formulation of said modified release bupropion hydrobrornide tablet, said modified release bupropion hydrobrornide tablet contains an increase in the amount of said 3-CBZ degradation product of no more than about 0.098 expressed in the percent increase of 3-CBZ degradation product relative to the amount of 3-CBZ degradation product present in said modified release bupropion hydrobromide tablet at said tablet formulation; and

wherein said increase in the amount of said 3-CBZ degradation product in said modifted release bupropion hydrobrornide tablet is less than respective percent increase of 3-CBZ degradation product that is present in an otherwise identical modified release tablet comprising an equivalent molar amount of bupropion hydrochloride at about 13 days and at about 20 days after formulation of said identical modified release bupropion hydrochloride tablet when the modified release bupropion hydrochloride tablet and said modified release bupropion hydrobromide tablet are each stored for at least about 13 days or at least about 20 days, respectively, at about 40 degrees C. and at about 75% relative humidity after tablet formulation.

2. The modified release bupropion hydrobromide tablet of claim 1, wherein said bupropion hydrobromide salt is present in an amount ranging from between about 40% to about 99% dry weight of said core, said binder is present in an amount ranging from between about 0.5% to about 25% dry weight of said core, and said lubricant is present in an amount ranging from between about 1% to about 6% dry weight of said core.

3. The modified release bupropion hydrobrornide tablet of claim 1, wherein the increase in the amount of said 3-CBZ degradation product contained in said modified release bupropion hydrobromide tablet after said modified release bupropion hydrobromide tablet formulation is stored for about 13 days is no more than about 0.035 percent and wherein the increase in the amount of said 3-CBZ degradation product contained in said modified release bupropion hydrobromide tablet after said modified release bupropion hydrobrornide tablet formulation is stored for about 20 days is no more than about 0.046 percent, and wherein said respective percent increases in 3-CBZ degradation product at about 13 days and at about 20 days in said modified release bupropion hydrobromide tablet are less than the respective percent increases in 3-CBZ degradation product in the otherwise identical modified release bupropion hydrochloride tablet after storage of the modified release bupropion hydrochloride tablet for about 13 and 20 days after formulation when each are stored after tablet formulation at about 40 degrees C. and at about 75% relative humidity.

4. A method of treating a depressive condition in a subject in need of bupropion administration comprising administering once daily to said subject a stable bupropion hydrobromide release tablet according to claim 1.

5. A method of treating a depressive condition in a subject in need of bupropion administration comprising administering once daily to said subject a stable bupropion hydrobromide release tablet according to claim 2.

6. A method of treating a depressive condition in a subject in need of bupropion administration comprising administering once daily to said subject a stable bupropion hydrobromide release tablet according to claim 3.

7. A method of treating a subject diagnosed with a depressive condition in need of bupropion administration comprising administering the stable bupropion hydrobromide modified release tablet according to claim 1.

8. A method of treating a subject diagnosed with a depressive condition in need of bupropion administration comprising administering the stable bupropion hydrobromide modified release tablet according to claim 3.

9. A method of treating a depressive condition in a subject in need of bupropion administration comprising administering once daily to said subject the stable bupropion hydrobromide modified release tablet according to claim 3.