Claims
- 1. Crystalline particles of escitalopram oxalate having a median particle size of at least 40 μm.
- 2. The crystalline particles of claim 1 wherein the medial particle size is from 50-200 μm.
- 3. A method for the manufacture of crystalline particles of escitalopram oxalate, which comprises
(a) dissolving escitalopram oxalate to form a solution of escitalopram oxalate; (b) gradually cooling the solution of escitalopram oxalate to a predetermined temperature while maintaining a controlled cooling rate; (c) adding crystals of escitalopram oxalate during the cooling of step (b); (d) holding the solution at the predetermined temperature; and (e) isolating crystalline particles of escitalopram oxalate from the solution.
- 4. The method of claim 3 wherein in step (a) escitalopram oxalate is dissolved in a solvent system.
- 5. The method of claim 3 wheren in step (c) the solution is cooled from a first temperature to a second temperature.
- 6. The method of claim 3 wherein the median particle size of the crystalline particles is at least 40 μm.
- 7. The method of claim 3 wherein the median particle size of the crystalline particles is from 50-200 μm.
- 8. The method of claim 4 wherein the solvent system comprises at least one alcohol and optionally water.
- 9. The method of claim 8 wherein the solvent system comprises ethanol.
- 10. The method of claim 4 wherein the solute:solvent weight ratio is between about 0.05:1 and 0.6:1.
- 11. The method of claim 4 wherein the solute:solvent weight ratio is between about 0.1:1 and 0.5:1.
- 12. The method of claim 4 wherein the solute:solvent weight ratio is between about 0.2:1 and 0.4:1.
- 13. The method of claim 5 wherein the first temperature is between about 50° C. and the refluxing temperature of the solvent system.
- 14. The method of claim 5 wherein the first temperature is between about 60° C. and the refluxing temperature of the solvent system.
- 15. The method of claim 5 wherein the first temperature is between about 70° C. and the refluxing temperature of the solvent system.
- 16. The method of claim 5 wherein the second temperature is between about 0° C. and 20° C.
- 17. The method of claim 5 wherein the second temperature is between about 0° C. and 15° C.
- 18. The method of claim 5 wherein the second temperature is between about 7° C. and 15° C.
- 19. The method of claim 3 wherein the controlled cooling rate comprises an initial cooling period during which the cooling rate does not exceed 0.6° C. per minute.
- 20. The method of claim 19 wherein the initial cooling period comprises the time between the start of the cooling period and the time at which the temperature is below 60° C.
- 21. The method of claim 19 wherein the initial cooling period comprises the time between the start of the cooling period and the time at which the temperature is below 50° C.
- 22. The method of claim 19 wherein the initial cooling period comprises the time between the start of the cooling period and the time at which the temperature is below 40° C.
- 23. The method of claim 19 wherein the cooling rate of the solution comprises from 0.2 to 0.4° C. per minute.
- 24. The method of claim 3 which comprises adding crystals of escitalopram oxalate at least two times during the cooling of step (b).
- 25. The method of claim 3 which comprises holding the solution at the predetermined temperature for at least one hour.
- 26. The method of claim 3 which comprises holding the solution at the predetermined temperature for 4 to 24 hours.
- 27. The method of claim 3, which comprises holding the solution at the predetermined temperature for 6 to 12 hours.
- 28. The method of claim 3, wherein step (e) comprises isolating the crystalline particles of escitalopram oxalate by solid/liquid separation techniques.
- 29. The method of claim 28, wherein the solid/liquid separation techniques comprise filtration.
- 30. A solid unit dosage form comprising the crystalline particles of escitalopram oxalate of claim 1.
- 31. A solid unit dosage form comprising the crystalline particles of escitalopram oxalate of claim 2.
- 32. The solid unit dosage form of claim 30, which comprises a tablet prepared by direct compression of a mixture of escitalopram oxalate and pharmaceutically acceptable excipients.
- 33. The solid unit dosage form of claim 32, wherein the tablet is coated.
- 34. The solid unit dosage form of claim 30, which is prepared by filling a hard gelatin capsule with a mixture of escitalopram oxalate and pharmaceutically acceptable excipients.
- 35. The solid unit dosage form of claim 30, which does not contain a binder.
- 36. The solid unit dosage form of claim 30, which comprises 1-30% w/w active ingredient calculated as escitalopram base.
- 37. The solid unit dosage form of claim 30, which comprises 4-20% w/w active ingredient calculated as escitalopram base.
- 38. The solid unit dosage form of claim 30, which comprises 6-10% w/w active ingredient calculated as escitalopram base.
- 39. The solid unit dosage form of claim 30, which further comprises a filler selected from the group consisting of lactose, sugars, calcium phosphates, starch, modified starches, microcrystalline cellulose, calcium sulfate and calcium carbonate.
- 40. The solid unit dosage form of claim 39, wherein the filler comprises a sugar selected from the group consisting of sorbitol, mannitol, dextrose and sucrose.
- 41. The solid unit dosage form of claim 39, wherein the filler comprises a calcium phosphate selected from the group consisting of dibasic, tribasic, hydrous and anhydrous calcium phosphate.
- 42. The solid unit dosage form of claim 39, wherein the filler comprises microcrystalline cellulose.
- 43. The solid unit dosage form of claim 42, wherein the microcrystalline cellulose is selected from the group consisting of ProSolv SMCC90 and Avicel PH 200.
- 44. The solid unit dosage form of claim 30, further comprising a lubricant.
- 45. The solid unit dosage form of claim 44, wherein the lubricant comprises a member selected from the group consisting of metallic stearates, stearic acid, wax, hydrogenated vegetable oil, talc and colloidal silica.
- 46. The solid unit dosage form of claim 45, wherein the lubricant comprises a metallic stearate selected from the group consisting of magnesium, calcium and sodium stearate.
- 47. The solid unit dosage form of claim 45, wherein the lubricant comprises a member selected from the group consisting of talc, magnesium stearate and calcium stearate.
- 48. The solid unit dosage form of claim 45, wherein the lubricant comprises talc and magnesium stearate.
- 49. The solid unit dosage form of claim 48, wherein the magnesium stearate is present in a weight percent of 0.4% to 2%, calculated on the weight of the solid dosage form.
- 50. The solid unit dosage form of claim 48, wherein the magnesium stearate is present in a weight percent of 0.7% to 1.4%, calculated on the weight of the solid dosage form.
- 51. The solid unit dosage form of claim 30, which is substantially free of lactose.
Priority Claims (1)
Number |
Date |
Country |
Kind |
PA 2001 01164 |
Jul 2001 |
DK |
|
Parent Case Info
[0001] This application is a continuation of International Application No. PCT/DKO2/00513 filed Jul. 25, 2002. The prior application is hereby incorporated by reference in its entirety.
Continuations (1)
|
Number |
Date |
Country |
Parent |
PCT/DK02/00513 |
Jul 2002 |
US |
Child |
10403453 |
Mar 2003 |
US |