Preparation of acid addition salts of amine bases by solid phase—gas phase reactions
A process for the preparation of an acid addition salt of an organic base comprising exposing the organic base in solid form to a gaseous acid, with the proviso that ziprasidone, its acid addition salts and intermediates thereof are excluded.
1. A process for the preparation of an acid addition salt of an organic base, which base is a medicine, comprising exposing the organic base in solid form to a gaseous acid at a temperature in the range of from about −50 to about 40° C., wherein reaction occurs between the solid base and the gaseous acid, with the proviso that ziprasidone, and its acid addition salts are excluded.
2. The process of claim 1 wherein the process is solvent free.
3. The process of claim 1 wherein the exposing the organic base in solid form to gaseous acid occurs in a dry environment.
4. The process of claim 1 further comprising agitation.
5. The process of claim 1 wherein the gaseous acid is mixed with one or more inert gases.
6. The process of claim 1 wherein the acid is a hydrogen halide.
7. The process of claim 6 wherein the hydrogen halide is selected from the group consisting of hydrogen chloride and hydrogen bromide.
8. The process of claim 1 wherein the gaseous acid is an organic acid.
9. The process of claim 8 wherein the organic acid is acetic acid.
10. A solvent free process for preparation of an acid addition salt of an organic base, which base is a medicine, comprising exposing, in a dry environment at a temperature in the range of from about −50° C. to about 40° C., the organic base in solid form to a gaseous acid mixed with one or more inert gases; agitating; and removal of excess acid, wherein reaction occurs between the solid base and the gaseous acid, with the proviso that ziprasidone, and its acid addition salts are excluded.
11. The process of claim 10 wherein the excess acid is collected and recycled.
12. The process of any one of claims 1 , 3 and 10 wherein the purity of the salt is substantially the same purity as the organic base.
13. The process of any one of claims 1 , 3 and 10 wherein the process is conducted in a pressurized reactor.
14. The process of claim 13 wherein the reactor is maintained at a pressure of about 0.1 atm to about 3 atm.
15. The process of claim 14 wherein the pressure is about 1.0 atm to about 2.0 atm.
16. The process of claim 14 wherein the pressure is increased gradually over a period of time.
17. The process of any one of claims 1 , 3 and 10 in which the medicine is selected from the group consisting of domperidone, terazosin, ranitidine and flecainide.
18. The process of claim 17 in which the organic base is domperidone.
19. The process of claim 17 in which the organic base is terazosin.
20. The process of claim 17 in which the organic base is ranitidine.
21. The process of claim 17 in which the organic base is flecainide.
22. The process of claim 12 wherein the organic base is a medicine selected from the group consisting of domperidone, terazosin, ranitidine and flecainide.
23. The process of any one of claims 1 , 3 and 10 wherein the organic base is an organic nitrogen base.