Preparation of risperidone

• US 20040229905A1
• Filed: 09/23/2003
• Published: 11/18/2004
• Est. Priority Date: 08/14/2000
• Status: Active Grant

• Current Assignee: Barnaba Krochmal, Ben-Zion Dolitzky, Dov Diller, Judith Aronhime
• Original Assignee: Barnaba Krochmal, Ben-Zion Dolitzky, Dov Diller, Judith Aronhime
• Inventors: Aronhime, Judith, Krochmal, Barnaba, Diller, Dov, Dolitzky, Ben-Zion
• Granted Patent: US 7,256,195 B2
• Time in Patent Office: Days
• US Class Current: 514/312
• CPC Class Codes: A61P 25/18 Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
• CPC Class Codes: C07D 471/04 Ortho-condensed systems

Abstract

The present invention is directed to the novel forms of risperidone, designated Form A, Form B and Form E. Methods for their preparation are also disclosed. The present invention also relates to processes for making risperidone. Pharmaceutical compositions containing the new forms of risperidone and methods of using them are also disclosed.

Claims

1-29. -29. (canceled)

30. A pharmaceutical formulation comprising risperidone form B with a pharmaceutically acceptable carrier and/or a pharmaceutically acceptable excipient, wherein the risperidone form B is characterized by x-ray powder diffraction peaks at 14.0±

0.2 and 21.7±

0.2 degrees two-theta .

32. The pharmaceutical formulation of claim 30, wherein the risperidone form B is further characterized by x-ray powder diffraction peaks at 10.8±

0.2, 11.9±

0.2, 12.6±

0.2, 14.0±

0.2, 17.5±

0.2, 18.3±

0.2, 19.9±

0.2, 21.0±

0.2, and 21.7±

0.2 degrees two-theta.

34. The pharmaceutical formulation of claim 30, 31, 32 or 33 wherein the pharmaceutical formulation is a dosage form suitable for oral administration or intravenous administration.

35. The pharmaceutical formulation of claim 34 wherein the dosage form is selected from the group consisting of tablet, coated pill, dragee, sachet, hard capsule, gelatin capsule, sub-lingual table, syrup and suspension.

36. A method for treating psychosis in a patient comprising administering to the patient the pharmaceutical formulation of claim 30, 32 or 33.

37. The method of claim 36, wherein the risperidone form B in the pharmaceutical formulation is administered at a daily dosage of about 4 to about 16 mg per day.

38. The method of claim 36, wherein the risperidone form B in the pharmaceutical formulation is administered at a daily dosage of about 4 to about 8 mg per day.

31. (canceled)

33. The A pharmaceutical formulation comprising risperidone form B with a pharmaceutically acceptable carrier and/or pharmaceutically acceptable excipient, wherein the risperidone form B is characterized by a x-ray powder diffraction pattern substantially as depicted in FIG. 2.

39. A pharmaceutical dosage formulation comprising an active ingredient and at least one component selected from the group consisting of pharmaceutical acceptable carriers and pharmaceutical acceptable excipients, wherein the active ingredient consists essentially of risperidone form B.

40. The pharmaceutical dosage formulation of claim 39 wherein the dosage formulation is in a form selected from the group consisting of tablet, coated pill, dragee, sachet, hard capsule, gelatin capsule, sub-lingual table, syrup and suspension.

41. A method of treating psychosis in a patient comprising administering to the patient the pharmaceutical dosage formulation of claim 39 or 40, wherein the risperidone form B in the pharmaceutical dosage formulation is administered at a daily dosage of about 4 to about 16 mg per day.

42. A pharmaceutical formulation comprising risperidone form A with a pharmaceutically acceptable carrier and/or a pharmaceutically acceptable excipient, wherein the risperidone form A is characterized by x-ray powder diffraction peaks at 14.0±

0.2 and 21.3±

0.2 degrees two-theta.

43. The pharmaceutical formulation of claim 42, wherein the risperidone form A is further characterized by x-ray powder diffraction peaks at 10.6±

0.2, 11.4±

0.2, 16.4±

0.2, 18.9±

0.2, 19.9±

0.2, 22.5±

0.2, 23.3±

0.2, 25.4±

0.2, 27.6±

0.2 and 29.0±

0.2 degrees two-theta.

45. The pharmaceutical formulation of claim 42, 43 or 44, wherein the pharmaceutical formulation is a dosage form suitable for oral administration or intravenous administration.

46. The pharmaceutical formulation of claim 45 wherein the dosage form is selected from the group consisting of tablet, coated pill, dragee, sachet, hard capsule, gelatin capsule, sub-lingual table, syrup and suspension.

47. A method for treating psychosis in a patient, comprising administering to the patient the pharmaceutical formulation of claim 42, 43 or 44.

48. The method of claim 47, wherein the risperidone form A in the pharmaceutical formulation is administered at a dose of about 4 to about 16 mg per day.

49. The method of claim 48, wherein the risperidone form A in the pharmaceutical formulation is administered at a dose of about 4 to about 8 mg per day.

44. A pharmaceutical formulation comprising risperidone form A with a pharmaceutically acceptable carrier and/or a pharmaceutically acceptable excipient, wherein the risperidone form A is characterized by a x-ray powder diffraction pattern substantially as depicted in FIG. 1.

50. A pharmaceutical dosage formulation comprising an active ingredient and at least one component selected from the group consisting of pharmaceutical acceptable carriers and pharmaceutical acceptable excipients, wherein the active ingredient consists essentially of risperidone form A characterized by x-ray powder diffraction peaks at 14.0±

0.2 and 21.3±

0.2 degrees two-theta.

51. The pharmaceutical dosage formulation of claim 50, wherein the dosage formulation is in a form selected from the group consisting of tablet, coated pill, dragee, sachet, hard capsule, gelatin capsule, sub-lingual table, syrup and suspension.

52. A method of treating psychosis in a patient, comprising administering to the patient the pharmaceutical dosage formulation of claim 50, wherein the risperidone form A in the pharmaceutical dosage formulation is administered at a dose of about 4 to about 16 mg per day.