MODIFIED RELEASE FORMULATIONS OF A BUPROPION SALT

• US 20080038345A1
• Filed: 07/06/2007
• Published: 02/14/2008
• Est. Priority Date: 06/27/2005
• Status: Active Grant

• Current Assignee: Valeant International (Barbados) Srl (Bausch Health Cos., Inc.)
• Original Assignee: Bioavail Laboratories
• Inventors: Massardo, Pietro, Jackson, Graham, Zhou, Fang, Maes, Paul, Oberegger, Werner, Turchetta, Stefano, Saleh, Mohammad
• Granted Patent: US 7,579,380 B2
• Time in Patent Office: Days
• US Class Current: 424/468
• 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 pharmaceutical composition, comprising:

at least one microparticle comprising at least one core which is surrounded by at least one osmotic subcoat, and at least one control-releasing coat which surrounds the at least one osmotic subcoat, wherein

said at least one core comprises bupropion hydrobromide and at least one excipient, and said at least one osmotic subcoat comprises at least one osmotic agent and at least one osmotic deposition vehicle.

2. The composition of claim 1, wherein the composition is an extended release composition.

3. The composition of claim 1, wherein the composition, when placed into a dissolution medium, provides a drug release profile wherein a predetermined lag time is substantially independent of the pH of the dissolution medium.

4. The composition of claim 1, wherein >

90% of the bupropion hydrobromide is released from the composition within 24 hours of placing the composition into an external environment of use, wherein the external environment of use is selected from the group consisting of a dissolution medium, the stomach, the small intestine, and the large intestine.

5. The composition of claim 1, wherein there is increased release of the bupropion hydrobromide from the composition within 24 hours of placing the composition into a first external environment of use compared to an otherwise identical or similar second composition comprising bupropion hydrobromide but not containing an osmotic subcoat placed into a second external environment of use,

wherein the first external environment of use and the second external environment of use are identical or similar, and

wherein each external environment of use is a dissolution medium.

6. The composition of claim 1, wherein the at least one control-releasing coat does not comprise a pore former.

7. The composition of claim 1, wherein >

90% of the bupropion hydrobromide is released from the composition within 24 hours of placing the composition into an external environment of use, wherein the at least one control-releasing coat does not comprise a pore former, and wherein the external environment of use is selected from the group consisting of a dissolution medium, the stomach, the small intestine, and the large intestine.

8. The composition of claim 1, wherein the at least one control-releasing coat does not comprise a pore former, wherein there is increased release of the bupropion hydrobromide from the composition within 24 hours of placing the composition into a first external environment of use compared to an otherwise identical or similar second composition comprising bupropion hydrobromide but not containing an osmotic subcoat placed into a second external environment of use,

wherein the first external environment of use and the second external environment of use are identical or similar, and

wherein each external environment of use is a dissolution medium.

9. The composition of claim 1, wherein the composition does not comprise a seal coat.

10. The composition of claim 1, wherein the at least one excipient is selected from the group consisting of a spheronization aid, a solubility enhancer, a disintegrating agent, a diluent, a lubricant, a binder, a filler, a suspending agent, an emulsifying agent, an anti-foaming agent, a falvouring agent, a colouring agent, a chemical stabilizer, a pH modifier, a swelling agent, and mixtures thereof.

11. The composition of claim 1, wherein the at least one excipient comprises a spheronization aid, and wherein the spheronization aid is selected from the group consisting of glyceryl monostearate, glyceryl behenate, glyceryl dibehenate, glyceryl palmitostearate, hydrogenated castor oil, magnesium stearate, calcium stearate, mannitol, sorbitol, xylitol, stearic acid, palmitic acid, sodium lauryl sulfate, PEG-32 distearate, PEG-150 distearate, cetostearyl alcohol, carnauba wax, white wax, paraffin wax, povidone, a cellulose ether, a polyvinylalcohol, and combinations thereof.

12. The composition of claim 1, wherein the at least one excipient comprises a solubility enhancer, and wherein the solubility enhancer is selected from the group consisting of a macrogol fatty acid ester, a polyethylene glycol, a polyethylene-polypropylene glycol, sorbitol, a propylene glycol, a pentaerythritol, and mixtures thereof.

13. The composition of claim 1, wherein the at least one excipient comprises a binder, and wherein the binder is selected from the group consisting of a hydrogenated vegetable oil, a castor oil, paraffin, an aliphatic alcohol, an alphatic acid, a long chain fatty acid, a fatty acid ester, a fatty alcohol, a fatty acid glyceride, a hydrogenated fat, a hydrocarbon, stearic acid, stearyl alcohol, a hydrophobic polymer having a hydrocarbon backbone, a hydrophilic polymers having a hydrocarbon backbone, modified starch, gelatin, polyvinylpyrrolidone, hydroxypropyl methylcellulose, hydroxypropyl cellulose, polyvinyl alcohol and mixtures thereof.

14. The composition of claim 1, wherein the at least one excipient comprises a lubricant, and wherein the lubricant is selected from the group consisting of glyceryl behenate, stearic acid, a hydrogenated vegetable oil, stearyl alcohol, leucine, polyethylene glycol, magnesium stearate, glyceryl monostearate, an ethylene oxide polymer, sodium lauryl sulfate, magnesium lauryl sulfate, sodium oleate, sodium stearyl fumarate, DL-leucine, colloidal silica, and mixtures thereof.

15. The composition of claim 1, wherein the at least one osmotic agent is selected from the group consisting of sodium chloride, sodium bromide, sodium bisulfate, potassium acid tartrate, citric acid, sodium citrate, fumaric acid, mannitol, sucrose, and mixtures thereof.

16. The composition of claim 1, wherein said at least one osmotic deposition vehicle is selected from the group consisting of a polyvinyl pyrrolidone, a hydroxyethyl cellulose, a hydroxypropyl cellulose, a low molecular weight hydroxypropyl methylcellulose (HPMC), a polymethacrylate, an ethyl cellulose and mixtures thereof.

17. The composition of claim 1, wherein the at least one osmotic deposition vehicle does not affect the rate and/or extent of release of the bupropion hydrobromide.

18. A method for controlling the rate and/or extent of release of bupropion hydrobromide from a composition, into an external environment of use, the composition comprising

at least one microparticle comprising at least one core which is surrounded by at least one osmotic subcoat, and at least one control-releasing coat which surrounds the at least one osmotic subcoat,

wherein said at least one core comprises bupropion hydrobromide and at least one excipient, and said at least one osmotic subcoat comprises at least one osmotic agent and at least one osmotic deposition vehicle,

wherein the method comprises at least one of the following:

controlling the amount of the at least one osmotic agent in the at least one osmotic subcoat, and

controlling the thickness of the at least one control-releasing coat, thereby controlling the release rate of the bupropion hydrobromide from the core of the microparticle into the external environment of use,

wherein the external environment of use is a dissolution medium.

19. A method of administering bupropion hydrobromide, the method comprising:

administering to a subject in need thereof a pharmaceutical composition, comprising;

at least one microparticle comprising at least one core which is surrounded by at least one osmotic subcoat, and at least one control-releasing coat which surrounds the at least one osmotic subcoat, wherein

said at least one core comprises bupropion hydrobromide and at least one excipient, and

said at least one osmotic subcoat comprises at least one osmotic agent and at least one osmotic deposition vehicle.

20. A pharmaceutical composition, comprising

at least one core which is surrounded by at least one osmotic subcoat,

at least one control-releasing coat which surrounds the at least one osmotic subcoat,

wherein the at least one core comprises bupropion hydrobromide and at least one excipient,

wherein the at least one osmotic subcoat comprises at least one osmotic agent and at least one osmotic deposition vehicle, and

a means for releasing the bupropion hydrobromide from the composition.