Pharmaceutical compositions
The invention provides (+)-α-dihydrotetrabenazine succinate salt. Also provided are (+)-α-dihydrotetrabenazine succinate salt for use in medicine, pharmaceutical compositions comprising (+)-α-dihydrotetrabenazine succinate salt and a pharmaceutically acceptable excipient and the uses of (+)-α-dihydrotetrabenazine succinate salt as a VMAT2 receptor antagonist and in the treatment of a movement disorder such as Tourette's syndrome. The invention further provides a method for preparing the (+)-α-dihydrotetrabenazine succinate salt.
1. A method of preparing (+)-α-dihydrotetrabenazine succinate salt which comprises mixing (+)-α-dihydrotetrabenazine free base and succinic acid together with a solvent, allowing time for (+)-α-dihydrotetrabenazine succinate salt to form and isolating the succinate salt.
2. The method according to claim 1 which comprises mixing the (+)-α-dihydrotetrabenazine free base and succinic acid together and then stirring the reaction mixture for a period of at least 1 hour.
3. The method according to claim 1 which comprises mixing the (+)-α-dihydrotetrabenazine free base and succinic acid together and then stirring the reaction mixture for a period of at least 2 hours.
4. The method according to claim 1 which comprises mixing the (+)-α-dihydrotetrabenazine free base and succinic acid together and then stirring the reaction mixture for a period of at least 12 hours.
5. The method according to claim 1 which comprises mixing the (+)-α-dihydrotetrabenazine free base and succinic acid together and then stirring the reaction mixture for a period of at least 1 day.
6. The method according to claim 1 wherein the solvent is a non-aqueous solvent.
7. The method according to claim 1 wherein the solvent consists of or contains at least one polar aprotic solvent.
8. The method according to claim 1 wherein the solvent consists of a polar aprotic solvent.
9. The method according to claim 7 wherein the polar aprotic solvent is selected from acetone, ethyl acetate and mixtures thereof.
10. The method according to claim 8 wherein the polar aprotic solvent is acetone or ethyl acetate.
11. The method according to claim 1 wherein the solvent is acetone.
12. The method according to claim 2 wherein the solvent is acetone.
13. The method according to claim 4 wherein the solvent is acetone.
14. The method according to claim 5 wherein the solvent is acetone.
15. The method according to claim 1 comprising mixing the (+)-α-dihydrotetrabenazine free base and succinic acid together in a molar ratio of about 1:1.
16. The method according to claim 4 comprising mixing the (+)-α-dihydrotetrabenazine free base and succinic acid together in a molar ratio of about 1:1.
17. The method according to claim 11 comprising mixing the (+)-α-dihydrotetrabenazine free base and succinic acid together in a molar ratio of about 1:1.
18. The method according to claim 1 wherein the (+)-α-dihydrotetrabenazine has an isomeric purity of greater than 90%.
19. The method according to claim 4 wherein the (+)-α-dihydrotetrabenazine has an isomeric purity of greater than 90%.
20. The method according to claim 11 wherein the (+)-α-dihydrotetrabenazine has an isomeric purity of greater than 90%.