Stable salts of olanzapine
View Patent ↗Several salts of olanzapine, including olanzapine malonate, olanzapine glycolate, olanzapine maleate, and olanzapine benzoate, have been found to have favorable solid state characteristics.
1. A salt of olanzapine selected from the group consisting of olanzapine malonate, olanzapine glycolate, and olanzapine benzoate.
2. The salt according to claim 1 , which is olanzapine hydrogen malonate.
3. The salt according to claim 1 , which is olanzapine monoglycolate
4. The salt according to claim 1 , which is olanzapine monobenzoate.
5. The salt of olanzapine according to claim 1 , wherein said salt is crystalline.
6. The salt according to claim 5 , which is substantially free from an organic solvent.
7. A pharmaceutical composition comprising said salt according to claim 1 and at least one pharmaceutically acceptable excipient.
8. The composition according to claim 7 , wherein said composition is a solid form.
9. The composition according to claim 7 , wherein said composition is a liquid form.
10. The composition according to claim 9 , which further comprises an acid.
11. A method, which comprises administering an antipsychotic effective amount of the olanzapine salt according to claim 1 to a patient in need thereof.
12. The method according to claim 11 , wherein said effective amount of olanzapine salt is within the range of 0.25 to 30 mg, expressed in terms of the weight of the free base.
13. A process which comprises reacting olanzapine and a pharmaceutically acceptable acid selected from the group consisting of malonic acid, glycolic acid, and benzoic acid in a solvent to form a pharmaceutically acceptable acid addition salt of olanzapine.
14. The process according to claim 13 , which further comprises precipitating said salt of olanzapine from said solvent.
15. The process according to claim 14 , which further comprises isolating said salt of olanzapine as a solvent-free salt.
16. The process according to claim 15 , wherein said solvent is acetone.
17. The process according to claim 14 , which further comprises converting said acid addition salt olanzapine to form olanzapine free base.
18. The process according to claim 17 , which further comprises purifying said addition salt of olanzapine prior to said converting to olanzapine free base.
19. The pharmaceutical composition according to claim 7 , wherein said salt is olanzapine benzoate and said excipient comprises anhydrous dibasic calcium phosphate.
20. The pharmaceutical composition according to claim 19 , wherein said composition further comprises hydroxypropyl cellulose.
21. The pharmaceutical composition according to claim 19 , wherein said composition is an uncoated tablet.
22. The pharmaceutical composition according to claim 20 , wherein said composition is a tablet tat was made by direct compression.