Rifaximin
Amorphous rifaximin, methods of making it, and pharmaceutical compositions containing it. Also described are methods of converting amorphous rifaximin to crystalline rifaximin and vice versa.
1. A process for the inter-conversion of crystalline rifaximin, said process comprising:
a) dissolving γ form rifaximin in a suitable solvent at 40-60° C.;
b) combining the solution with water and allowing to cool;
c) filtering and washing the resulting solid, and
d) drying the resulting solid at a temperature from 80-110° C. to obtain the β form of rifaximin.
2. The process according to claim 1 , wherein the suitable solvent is a water miscible solvent.
3. The process according to claim 2 , wherein the water miscible solvent is acetone, acetonitrile, lower alcohols or mixtures thereof.
4. The process according to claim 3 , wherein the water miscible solvent is acetonitrile.
5. A process for converting amorphous rifaximin to crystalline γ form rifaximin, said process comprising dissolving amorphous rifaximin in an organic solvent, then drying the rifaximin mixture at a temperature from 100 to 110° C. to yield γ form rifaximin.
6. The process according to claim 5 , wherein the rifaximin is dissolved in the organic solvent at 40-60° C., combined with water, allowed to cool, and filtered and washed with a mixture of organic acid and water.
7. A process for converting amorphous rifaximin to crystalline β form rifaximin, said process comprising combining the amorphous rifaximin with a mixture of a water-miscible organic solvent and water, then drying the rifaximin mixture at a temperature from 80 to 110° C. for 10-15 hours to yield β form rifaximin.
8. The process according to claim 7 , wherein the water-miscible organic solvent comprises acetone, acetonitrile, or one or more C 1-4 alcohols.
9. The process according to claim 7 , wherein the water-miscible organic solvent is isopropyl alcohol.
10. The process according to claim 7 , wherein prior to combining the amorphous rifaximin with the mixture of organic solvent and water, the amorphous rifaximin is dissolved in an organic solvent at 40-60° C. combined with water, allowed to cool, and filtered to produce a rifaximin residue which is combined with the water miscible solvent and water.
11. A process for converting a crystalline form of rifaximin to an amorphous form of rifaximin, said process comprising:
(i) dissolving the crystalline rifaximin in a suitable solvent,
(ii) filtering and washing the filtrate with a suitable solvent,
(iii) concentrating the residue at 40-60° C. to form a rifaximin residue,
(iv) stripping rifaximin residue with n-heptane;
(v) filtering and washing the solid with n-heptane; and
(vi) drying the solid at a temperature below 40° C. to obtain amorphous rifaximin.
12. The process according to claim 11 , wherein the amorphous rifaximin has an XRPD as shown in FIG. 1 .
13. The process according to claim 11 , wherein the amorphous rifaximin is substantially free of any crystalline rifaximin.
14. The process according to claim 11 , wherein the amorphous rifaximin is formulated into a solid oral pharmaceutical product.