Claims
- 1. A pharmaceutical tablet composition comprising an effective amount of amlodipine free base and at least one pharmaceutically acceptable excipient;
wherein said tablet exhibits low punch residue.
- 2. The composition according to claim 1, wherein said tablet leaves an average residue on the tablet punch of 0.7 μg·cm−2 per tablet or less.
- 3. The composition according to claim 1, wherein said excipient is a calcium phosphate.
- 4. The composition according to claim 1, wherein said excipient is microcrystalline cellulose.
- 5. The composition according to claim 3, which further comprises microcrystalline cellulose.
- 6. The composition according to claim 5, wherein said calcium phosphate is anhydrous calcium hydrogen phosphate.
- 7. The composition according to claim 1, wherein said amlodipine free base is crystalline form II amlodipine free base.
- 8. The composition according to claim 1, wherein said amlodipine free base is amorphous amlodipine free base.
- 9. The composition according to claim 1, wherein said amlodipine is a mixture of crystalline amlodipine free base form I and form II.
- 10. The composition according to claim 1, wherein said tablet contains 1 to 100 mg of said amlodipine free base.
- 11. Crystalline amlodipine free base of form II.
- 12. A method of treating or preventing hypertension, angina, or congestive heart failure, which comprises administering an effective amount of amlodipine free base to a patient in need thereof.
- 13. A process which comprises:
deprotecting an N-protected amlodipine with a deprotecting agent to form amlodipine free base; precipitating said amlodipine free base from a solution; and isolating said precipitated amlodipine free base in solid state form.
- 14. The process according to claim 13, wherein said solution is formed by said deprotecting step.
- 15. The process according to claim 14, wherein said solution contains water.
- 16. The process according to claim 13, wherein said N-protected amlodipine is phthalodipine of formula (2a):
- 17. The process according to claim 16, wherein said deprotecting agent is aqueous methylamine.
- 18. The process according to claim 13, wherein said deprotecting step occurs in an aqueous solution or slurry.
- 19. The process according to claim 18, which further comprises extracting said amlodipine free base in a water immiscible solvent to form said solution.
- 20. The process according to claim 19, wherein said water immiscible solvent is toluene.
- 21. The process according to claim 13, wherein said precipitation is a crystallization step.
- 22. The process according to claim 21, wherein said crystallization comprises cooling said solution.
- 23. The process according to claim 22, wherein said crystallization additionally comprises evaporating a portion of the solvent from said solution.
- 24. The process according to claim 21, wherein said crystallization comprises adding a contra-solvent to said solution.
- 25. The process according to claim 22, wherein said crystallization begins at a temperature above 5° C.
- 26. The process according to claim 22, wherein said crystallization begins at a temperature of 5° C. or less and said solution is based on a non-aqueous solvent.
- 27. The process according to claim 13, wherein said isolated amlodipine free base is crystalline form I amlodipine free base.
- 28. The process according to claim 13, wherein said isolated amlodipine free base is crystalline form II amlodipine free base.
- 29. The process according to claim 13, which further comprises dissolving said isolated amlodipine free base in a non-aqueous purification solvent and crystallizing said dissolved free base from said purification solvent to form purified crystalline amlodipine free base.
- 30. A process for purifying amlodipine free base, which comprises: crystallizing amlodipine free base from a non-aqueous solvent.
- 31. The process according to claim 30, wherein said crystallization produces amlodipine free base crystals having an average particle size of 150 to 350 microns.
- 32. A population of particulate amlodipine free base having an average particle size of at least 100 microns.
- 33. The population according to claim 32, wherein said particles are crystals.
- 33. The population according to claim 33, wherein said average particle size is 150 to 350 microns.
Parent Case Info
[0001] This application claims the benefit of priority under 35 U.S.C. §119(e) from provisional patent application Serial No. 60/258,613, filed Dec. 29, 2000.
Provisional Applications (1)
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Number |
Date |
Country |
|
60258613 |
Dec 2000 |
US |