Modified release formulations of a bupropion salt

• US 20070027213A1
• Filed: 06/27/2006
• Published: 02/01/2007
• Est. Priority Date: 06/27/2005
• Status: Active Grant

• Current Assignee: Valeant International (Barbados) Srl (Bausch Health Cos., Inc.)
• Original Assignee: Biovail Laboratories International Srl (Bausch Health Cos., Inc.)
• Inventors: Massardo, Pietro, Jackson, Graham, Zhou, Fang, Maes, Paul, Oberegger, Werner, Turchetta, Stefano, Ashty, Mohammad
• Granted Patent: US 7,241,805 B2
• Time in Patent Office: Days
• US Class Current: 514/563
• 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

1-83. -83. (canceled)

84. A stable bupropion pharmaceutical composition suitable for oral administration to a subject in need of bupropion therapy for treatment of a condition or palliating a disorder, comprising:

an effective amount of bupropion hydrobromide for treatment of the condition or palliating the disorder,

wherein the bupropion hydrobromide salt contained in said pharmaceutical composition is more stable than an otherwise identical pharmaceutical composition comprising the equivalent molar amount of a bupropion hydrochloride salt when each are stored for at least about 3 months at about 40 degrees C. and at about 75% relative humidity.

85. The stable bupropion pharmaceutical composition of claim 84 wherein said bupropion hydrobromide salt is more stable than an otherwise identical pharmaceutical composition containing bupropion hydrochloride when each are stored for at least about 6 months at about 40 degrees C. and at about 75% relative humidity.

86. The stable bupropion pharmaceutical composition of claim 84 which contains less of at least one degradation product characteristic of bupropion degradation after being stored at about 40 degrees C. at about 75% relative humidity than an otherwise identical pharmaceutical composition containing bupropion hydrochloride when stored under the same conditions.

87. The stable bupropion pharmaceutical composition of claim 84 which exhibits less fluctuations in the in vitro dissolution profile in at least one dissolution media than an otherwise identical pharmaceutical composition containing bupropion hydrochloride after each are stored for at least about 3 months at about 40 degrees C. and at about 75% relative humidity.

88. The stable bupropion pharmaceutical composition of claim 84 which is in the form of a tablet.

89. The stable bupropion pharmaceutical composition of claim 88, wherein the tablet is a modified release tablet.

90. The stable bupropion pharmaceutical composition of claim 89, wherein the modified release tablet is suitable for once daily oral administration.

91. The stable bupropion pharmaceutical composition of any one of claims 84-90 which comprises about 174 or about 348 mg of bupropion hydrobromide.

93. The stable bupropion pharmaceutical composition of claim 84, wherein the condition or disorder is selected from a group consisting of depression, smoking cessation, obesity and seasonal affective disorder.

92. The stable bupropion pharmaceutical composition of claim go, wherein said stable bupropion pharmaceutical composition comprises from about 50 mg to about 500 mg of bupropion HBr.

94. A method of treating a subject in need of bupropion therapy, said method comprises

orally administering a stable bupropion pharmaceutical composition comprising an effective amount of bupropion hydrobromide to the subject in need thereof,

wherein the bupropion hydrobromide salt in said pharmaceutical composition is more stable when stored for at least about 3 months at about 40 degrees C. and at about 75% relative humidity than an otherwise identical pharmaceutical composition containing an equivalent molar amount of bupropion hydrochloride.

95. The method of claim 94, wherein said method is used to treat a condition selected from a group consisting of depression, smoking cessation, obesity and seasonal affective disorder.

96. The method of claim 94, wherein the pharmaceutical composition is more stable than an otherwise identical pharmaceutical composition containing bupropion hydrochloride when each is stored for at least about 6 months at about 40 degrees C. and at about 75% relative humidity.

97. The method of claim 94, wherein said pharmaceutical composition contains less of at least one degradation product characteristic of bupropion degradation after being stored for at least about 3 months at about 40 degrees C. and at about 75% relative humidity than an otherwise identical pharmaceutical composition containing the same molar amount of bupropion hydrochloride.

98. The method of claim 94, wherein the pharmaceutical composition exhibits less fluctuations in the in vitro dissolution profile than an otherwise identical pharmaceutical composition containing the equivalent molar amount of bupropion hydrochloride after each are stored for at least about 3 months at about 40 degrees C. and at about 75% relative humidity.

99. The method of claim 94, wherein the pharmaceutical composition is in an oral dosage form.

100. The method of claim 99, wherein the oral dosage form is selected from the group consisting of a tablet or capsule.

101. The method of claim 100, wherein the pharmaceutical composition comprises about 174 or about 348 mg of bupropion hydrobromide.

102. The method of claim 94, wherein the pharmaceutical composition comprises from about 50 to about 500 mg of bupropion hydrobromide.

103. The method of any one of claims 99-102, wherein the stable bupropion pharmaceutical composition is a modified release composition.

104. The method of claim 103, wherein said administration step comprises administering the stable bupropion pharmaceutical composition to the subject once daily.