Olanzapine dihydrate D

• US 6,251,895 B1
• Filed: 09/23/1997
• Issued: 06/26/2001
• Est. Priority Date: 09/23/1996
• Status: Expired due to Fees

• Current Assignee: Eli Lilly and Company
• Original Assignee: Eli Lilly and Company
• Inventors: Nichols, John Richard, Reutzel, Susan Marie, Stephenson, Gregory Alan, Larsen, Samuel Dean
• Primary Examiner(s): Webman, Edward J.
• Application Number:
  US08/935,883
• Time in Patent Office: 1,372 Days
• Field of Search: 424/464, 514/220, 540/557
• US Class Current: 514/220
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/18 Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
• CPC Class Codes: A61P 25/22 Anxiolytics
• CPC Class Codes: A61P 25/24 Antidepressants
• CPC Class Codes: C07D 495/04 Ortho-condensed systems

Abstract

The present invention provides the novel Dihydrate D 2-methyl-thieno-benzodiazepine and a formulation therefor.

Claims

1. Olanzapine dihydrate D, which has an X-ray powder diffraction pattern with the following interplanar spacings (d) in Angstroms:

2. Olanzapine dihydrate D as claimed in claim 1 wherein the interplanar spacings have the following relative intensities (I/I₁)

3. Olanzapine dihydrate D of claim 1 in substantially pure form.

4. Olanzapine dihydrate D of claim 2 in substantially pure form.

5. Olanzapine dihydrate D of claim 4 which contains less than 2% olanzapine dihydrate B.

6. A pharmaceutical formulation comprising as an active ingredient olanzapine dihydrate D of claim 1 and a pharmaceutically acceptable carrier, diluent, or excipient.

7. A pharmaceutical formulation comprising as an active ingredient olanzapine dihydrate D of claim 2 and a pharmaceutically acceptable carrier, diluent, or excipient.

8. A pharmaceutical formulation comprising as an active ingredient olanzapine dihydrate D of claim 3 and a pharmaceutically acceptable carrier, diluent, or excipient.

9. A formulation of claim 6 wherein the formulation is an aqueous suspension.

10. A formulation of claim 6 wherein the formulation is a tablet.

11. A formulation of claim 8 wherein the formulation is an aqueous suspension.

12. A method for treating a psychotic condition in a mammal comprising administering an effective amount of olanzapine dihydrate D of claim 1 to the mammal.

13. A method for treating a condition selected from the group consisting of anxiety, schizophrenia, schizophreniform disorder, a functional bowel disorder, and psychosis in a mammal, comprising administering an effective amount of olanzapine dihydrate D of claim 1 to the mammal.

14. A process for preparing a crystalline olanzapine dihydrate D comprising stirring technical grade olanzapine in an aqueous solvent from about one hour to about six days until dihydrate D is formed.

15. The process of claim 14 wherein the olanzapine is stirred for at least 12 hours.

16. The process of claim 15 wherein the olanzapine is stirred for at least 24 hours.

17. The process of claim 16 wherein the olanzapine is stirred for about 5 days.

18. The process of claim 14 wherein the solvent includes a wetting agent.

19. The process of claim 14 which includes the additional step of drying the dihydrate D using a technique sufficiently mild to avoid desolvation of the dihydrate D.

20. Olanzapine dihydrate D having an X-ray powder diffraction pattern with the following interplanar spacings (d) in Angstroms:

9.45, 7.45, 5.22, 4.40, 4.35 &

4.28.

21. Olanzapine dihydrate D having an X-ray powder diffraction pattern with the following interplanar spacings (d) in Angstroms:

9.45, 7.71, 7.45, 5.22, 4.98, 4.78, 4.40, 4.35, 4.28 &

3.38.