Preparation of risperidone

• US 7,256,195 B2
• Filed: 09/23/2003
• Issued: 08/14/2007
• Est. Priority Date: 08/14/2000
• Status: Expired due to Fees

• Current Assignee: Teva Pharmaceutical Industries Limited
• Original Assignee: Teva Pharmaceutical Industries Limited
• Inventors: Aronhime, Judith, Krochmal, Barnaba, Diller, Dov, Dolitzky, Ben-Zion
• Primary Examiner(s): COLEMAN, BRENDA LIBBY
• Application Number:
  US10/669,272
• Publication Number:
  US 20040229905A1
• Time in Patent Office: 1,421 Days
• Field of Search: 514/259.41, 544/282
• US Class Current: 514/259.41
• 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. A solid or solid-containing pharmaceutical formulation comprising a crystalline form of risperidone with a pharmaceutically acceptable carrier and/or a pharmaceutically acceptable excipient, wherein the crystalline form of risperidone is characterized by x-ray powder diffraction peaks at 14.0±

0.2 and 21.7±

0.2 degrees two-theta.

2. The solid or solid-containing pharmaceutical formulation of claim 1, wherein the crystalline form of risperidone 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.

4. The solid or solid-containing pharmaceutical formulation of claim 1, 2 or 3 wherein the solid or solid-containing pharmaceutical formulation is in a dosage form suitable for oral administration or intravenous administration.

5. The solid or solid-containing pharmaceutical formulation of claim 4 wherein the dosage form is selected from the group consisting of a tablet, compressed pill, coated pill, dragee, sachet, hard capsule, gelatin capsule, sub-lingual tablet, and suspension, wherein the crystalline form of risperidone in the suspension is solid.

6. A method for treating psychosis in a patient comprising administering to the patient the solid or solid-containing pharmaceutical formulation of claim 1, 2 or 3.

7. The method of claim 6, wherein the crystalline form of risperidone in the solid or solid-containing pharmaceutical formulation is administered at a daily dosage of about 4 to about 16 mg per day.

8. The method of claim 6, wherein the crystalline form of risperidone in the solid or solid-containing pharmaceutical formulation is administered at a daily dosage of about 4 to about 8 mg per day.

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

9. A solid or solid-containing 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 a crystalline form of risperidone characterized by x-ray powder diffraction peaks at 14.0±

0.2 and 21.7±

0.2 degrees two-theta.

10. The solid or solid-containing pharmaceutical dosage formulation of claim 9 wherein the dosage formulation is in a form selected from the group consisting of a tablet, compressed pill, coated pill, dragee, sachet, hard capsule, gelatin capsule, sub-lingual tablet and suspension, wherein the crystalline form of risperidone in the suspension is solid.

11. A method of treating psychosis in a patient comprising administering to the patient the solid or solid-containing pharmaceutical dosage formulation of claim 9 or 10, wherein the crystalline form of risperidone in the pharmaceutical dosage formulation is administered at a daily dosage of about 4 to about 16 mg per day.

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

0.2 and 21.3±

0.2 degrees two-theta.

13. The solid or solid-containing pharmaceutical formulation of claim 12, wherein the crystalline form of risperidone 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.

15. The solid or solid-containing pharmaceutical formulation of claim 12, 13 or 14, wherein the pharmaceutical formulation is in a dosage form suitable for oral administration or intravenous administration.

16. The solid or solid-containing pharmaceutical formulation of claim 15, wherein the dosage form is selected from the group consisting of a tablet, compressed pill, coated pill, dragee, sachet, hard capsule, gelatin capsule, sub-lingual tablet and suspension, wherein the crystalline form of risperidone in the suspension is solid.

17. A method for treating psychosis in a patient, comprising administering to the patient the solid or solid-containing pharmaceutical formulation of claim 12, 13 or 14.

18. The method of claim 17, wherein the crystalline form of risperidone in the solid or solid-containing pharmaceutical formulation is administered at a dose of about 4 to about 16 mg per day.

19. The method of claim 18, wherein the crystalline form of risperidone in the solid or solid-containing pharmaceutical formulation is administered at a dose of about 4 to about 8 mg per day.

14. A solid or solid-containing pharmaceutical formulation comprising a crystalline form of risperidone with a pharmaceutically acceptable carrier and/or a pharmaceutically acceptable excipient, wherein the crystalline form of risperidone is characterized by a x-ray powder diffraction pattern sub stantially as depicted in FIG. 1.

20. A solid or solid-containing 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 a crystalline form of risperidone characterized by x-ray powder diffraction peaks at 14.0±

0.2 and 21.3±

0.2 degrees two-theta.

21. The solid or solid-containing pharmaceutical dosage formulation of claim 20, wherein the dosage formulation is in a form selected from the group consisting of a tablet, coated pill, compressed pill, dragee, sachet, hard capsule, gelatin capsule, sub-lingual tablet and suspension, wherein the crystalline form of risperidone in the suspension is solid.

22. A method of treating psychosis in a patient, comprising administering to the patient the solid or solid-containing pharmaceutical dosage formulation of claim 20, wherein the crystalline form of risperidone in the pharmaceutical dosage formulation is administered at a dose of about 4 to about 16 mg per day.