Details for Patent: 7,772,273

Title:	Stabilized atorvastatin
Abstract:	A stable pharmaceutical composition for oral administration comprising atorvastatin and an amount of a pharmaceutically acceptable organic alkalizing compound capable of establishing a microenvironment for atorvastatin having a pH of at least about 5, for example 2-amino-2-(hydroxymethyl)-1,3-propanediol (trometamol).
Inventor(s):	Holm; Per (Vanlose, DK)
Assignee:	LifeCycle Pharma A/S (Horsholm, DK)
Filing Date:	Feb 09, 2007
Application Number:	11/673,270
Claims:	1. A stable pharmaceutical composition for oral administration comprising atorvastatin or a pharmaceutically acceptable salt thereof and an amount of a pharmaceutically acceptable organic alkalizing compound capable of establishing a micro-environment for atorvastatin having a pH of at least about 5, wherein the composition is free of other stabilizing compounds, the organic alkalizing compound is present in an amount ranging from 0.01 to 0.5% w/w, and the composition comprises less than 0.2% w/w of atorvastatin lactone after 6 months storage at 25.degree. C. at 60% relative humidity. 2. The pharmaceutical composition according to claim 1, wherein the organic alkalizing compound is selected from the group consisting of amines, amides and ammonium compounds. 3. The pharmaceutical composition according to claim 1, wherein the alkalizing compound is selected from the group consisting of ammonium lactate, ammonium bicarbonate, mono ethanolamine, di ethanolamine, tri ethanolamine, tri hydroxymethylaminomethane, ethylenediamine, N-methyl glucamide, 6N-methyl glucamine, meglucamine, L-lysine and 2-amino-2-(hydroxymethyl)-1,3-propanediol. 4. The pharmaceutical composition according to claim 1, wherein the alkalizing compound is 2-amino-2-(hydroxymethyl)-1,3-propanediol (tromethamine). 5. The pharmaceutical composition according to claim 1, which is free of antioxidants. 6. The pharmaceutical composition according to claim 4, comprising from 0.02% w/w to 1.0% w/w of tromethamine. 7. The pharmaceutical composition according to claim 4, comprising tromethamine in an amount below 0.5% w/w. 8. The pharmaceutical composition according to claim 1, wherein the atorvastatin is selected from the group consisting of crystalline atorvastatin calcium, amorphous atorvastatin calcium, crystalline atorvastatin magnesium, amorphous atorvastatin magnesium, a mixture of amorphous and crystalline atorvastatin calcium and a mixture of amorphous and crystalline atorvastatin magnesium. 9. The pharmaceutical composition according to claim 1, wherein the atorvastatin is crystalline atorvastatin magnesium. 10. A tablet comprising atorvastatin or a pharmaceutically acceptable salt thereof and tromethamine, wherein the tablet is free of other stabilizing compounds, and the tablet comprises less than 0.5% w/w of tromethamine and less than 0.2% w/w of atorvastatin lactone after 6 months storage at 25.degree. C. at 60% relative humidity. 11. A method for preparing a tablet comprising atorvastatin and an amount of a pharmaceutically acceptable organic alkalizing compound capable of establishing a microenvironment for atorvastatin having a pH of at least about 5, which method comprises the steps of: i) preparing a solid pharmaceutical composition by wet granulation of atorvastatin and the alkalizing compound, and iii) compressing the composition into a tablet, wherein the composition is free of other stabilizing compounds.