Pharmaceutical compositions containing new polymorphic forms of olanzapine and uses thereof

• US 7,022,698 B2
• Filed: 12/27/2001
• Issued: 04/04/2006
• Est. Priority Date: 12/28/1999
• Status: Expired due to Fees

• Current Assignee: Cipla (EU) Limited (Cipla Limited)
• Original Assignee: U & I Pharmaceuticals, Ltd.
• Inventors: Rao, Dharmaraj R., Kankan, Rajendra N., Hamied, Yusuf K.
• Primary Examiner(s): COLEMAN, BRENDA LIBBY
• Application Number:
  US10/026,949
• Publication Number:
  US 20020165225A1
• Time in Patent Office: 1,559 Days
• Field of Search: 514/220, 540/557
• US Class Current: 514/220
• CPC Class Codes: A61K 31/551 having two nitrogen atoms, e.g. dilazep
• CPC Class Codes: A61P 25/18 Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
• CPC Class Codes: C07D 495/04 Ortho-condensed systems

Abstract

Pharmaceutical compositions containing Form III, Form IV, Form V olanzapine and/or pharmaceutically acceptable salts thereof. The pharmaceutical compositions are useful for the treatment of psychotic conditions, mild anxiety and gastrointestinal conditions. In particular, the compositions are useful for treating schizophrenia and related disorders, acute mania, Bipolar I Disorder, psychotic mood disorder and psychosis in patients with Alzheimer'"'"'s disease.

Claims

1. A pharmaceutical composition comprising as an active ingredient at least one solid olanzapine polymorph selected from Form III olanzapine, Form IV olanzapine, Form V olanzapine, and salts and mixtures thereof;

and

one or more pharmaceutically acceptable carriers, excipients or diluents;

wherein Forms III, IV and V olanzapine are olanzapine polymorphs having typical x-ray powder diffraction patterns represented by the following interplanar spacings;

FORM-IIIFORM-IVFORM IVd-spacing (Å

)d-spacing (Å

)d-spacing (Å

)10.31569.948710.59327.17138.507410.21706.50148.21039.95035.51654.81728.52594.85414.71147.10164.55784.61226.07314.49384.52825.20414.45364.23404.98564.25884.09014.81533.98983.75744.75143.72883.69894.53023.56264.47143.02624.22714.13073.98803.77633.71673.5315.

and the composition is in the form of a suspension, emulsion, solid capsule, tablet, caplet, cachet, lozenge, troche, granular formulation or powdered formulation.

2. The pharmaceutical composition according to claim 1, wherein the olanzapine polymorph is Form III olanzapine.

3. The pharmaceutical composition according to claim 2, wherein the Form III olanzapine is further characterized bysubstantially the following x-ray powder diffraction pattern, wherein d represents the interplanar spacing and I/I₁ represents the typical relative intensities:

d-spacing (Å

)I/I₁10.3156100 

7.1713166.5014175.5165244.8541464.5578244.4938384.4536364.2588493.9898523.7288423.5626253.0262 

18.

4. The pharmaceutical composition according to claim 2, wherein the Form III olanzapine is further characterized by having an infrared spectrum having absorbances at the following wavenumbers:

611

656

671

746

765

845

935

1369.

5. The pharmaceutical composition according to claim 1, wherein the olanzapine polymorph is Form IV olanzapine.

6. The pharmaceutical composition according to claim 5, wherein the Form IV olanzapine is further characterized by substantially the following x-ray powder diffraction pattern, wherein d represents the interplanar spacing and I/I₁ represents the typical relative intensities:

d-spacing (Å

)I/I₁9.9487838.5074158.2103174.8172100 

4.7114414.6122354.5282334.2340294.0901323.7574233.6989 

40.

7. The pharmaceutical composition according to claim 5, wherein the Form IV olanzapine is further characterized by having an infrared spectrum having absorbances at the following wavenumbers:

604

661

758

904

931

1365

1456.

8. The pharmaceutical composition according to claim 1, wherein the olanzapine polymorph is Form V olanzapine.

9. The pharmaceutical composition according to claim 8, wherein the Form V olanzapine is further characterized by substantially the following x-ray powder diffraction pattern, wherein d represents the interplanar spacing and I/I₁ represents the typical relative intensities:

d-spacing (Å

)I/I₁10.59321710.2170100 

9.9503578.5259227.1016176.0731175.2041194.9856204.8153624.7514344.5302244.4714514.2271914.1307403.9880313.7763103.7167623.5315 

22.

10. The pharmaceutical composition according to claim 8, wherein the Form V olanzapine is further characterized by having an infrared spectrum having absorbances at the following wavenumbers:

604

671

746

758

847

928

1357

1369.

11. A pharmaceutical composition containing as an active ingredient at least one solid olanzapine polymorph selected from Form III olanzapine, Form IV olanzapine, Form V olanzapine, and salts and mixtures thereof;

wherein Forms III, IV and V olanzapine are olanzapine polymorplis having typical x-ray powder diffraction patterns represented by the following interplanar spacings;

FORM-IIIFORM-IVFORM-Vd-spacing (Å

)d-spacing (Å

)d-spacing (Å

)10.31569.948710.59327.17138.507410.21706.50148.21039.95035.51654.81728.52594.85414.71147.10164.55784.61226.07314.49384.52825.20414.45364.23404.98564.25884.09014.81533.98983.75744.75143.72883.69894.53023.56264.47143.02624.22714.13073.98803.77633.71673.5315

and the composition is in the form of a suspension, emulsion, solid capsule, tablet, caplet, cachet, lozenge, troche, granular formulation or powdered formulation.

12. A method of treating a patient having a psychotic condition or mild anxiety comprising administering a therapeutically effective amount of at least one olanzapine polymorph to said patient;

wherein the at least one olanzapine polymorph is selected from Form III olanzapine, Form IV olanzapine, Form V olanzapine, and salts and mixtures thereof; and

wherein Forms III, IV and V olanzapine are olanzapine polymorphs having typical x-ray powder diffraction patterns represented by the following interplanar spacings;

FORM-IIIFORM-IVFORM IVd-spacing (Å

)d-spacing (Å

)d-spacing (Å

)10.31569.948710.59327.17138.507410.21706.50148.21039.95035.51654.81728.52594.85414.71147.10164.55784.61226.07314.49384.52825.20414.45364.23404.98564.25884.09014.81533.98983.75744.75143.72883.69894.53023.56264.47143.02624.22714.13073.98803.77633.71673.5315.

13. The method according to claim 12, wherein the olanzapine polymorph is Form III olanzapine.

14. The method according to claim 12, wherein the olanzapine polymorph is Form IV olanzapine.

15. The method according to claim 12, wherein the olanzapine polymorph is Form V olanzapine.

16. A method of treating a patient having a psychotic condition selected from schizophrenia and schizophreniform disorders, acute mania, Bipolar I Disorder, psychotic mood disorder and psychosis associated with Alzheimer'"'"'s disease comprising administering a therapeutically effective amount of at least one olanzapine polymorph to said patient;

wherein the at least one olanzapine polymorph is selected from Form III olanzapine, Form IV olanzapine, Form V olanzapine, and salts and mixtures thereof and

wherein Forms III, IV and V olanzapine are olanzapine polymorphs having typical x-ray powder diffraction patterns represented by the following interplanar spacings;

FORM-IIIFORM-IVFORM IVd-spacing (Å

)d-spacing (Å

)d-spacing (Å

)10.31569.948710.59327.17138.507410.21706.50148.21039.95035.51654.81728.52594.85414.71147.10164.55784.61226.07314.49384.52825.20414.45364.23404.98564.25884.09014.81533.98983.75744.75143.72883.69894.53023.56264.47143.02624.22714.13073.98803.77633.71673.5315.

17. The method according to claim 16, wherein the olanzapine polymorph is Form III olanzapine.

18. The method according to claim 16, wherein the olanzapine polymorph is Form IV olanzapine.

19. The method according to claim 16, wherein the olanzapine polymorph is Form V olanzapine.