Crystalline fosamprenavir calcium and process for the preparation thereof
The main object of the present invention relates to a novel crystalline form of Fosemprenavir Calcium designated as Form A. Another object of the present invention relates to a process for the preparation of Crystalline Form A of Fosemprenavir Calcium. Yet another object of the present invention relates to crystalline Forma A of Fosemprenavir Calcium characterized by a PXRD diffraction having reflections at about 3.1±0.2, 4.4±0.2, 5.0±0.2, 6.3±0.2, 7.4±0.2, 8.0±0.2, 2θ.
1. Crystalline fosamprenavir calcium form A characterized by a powder X-ray diffraction pattern as shown in FIG. 1 .
2. Crystalline fosamprenavir calcium form A having a powder X-ray diffraction pattern having at least one characteristic peak at 4.4±0.2, 5.0±0.2, 6.3±0.2, 7.4±0.2, or 8.0±0.2 2Θ.
3. A process for the preparation of crystalline fosamprenavir calcium form A comprising the steps of:
a) dissolving fosamprenavir calcium salt in a solvent system;
b) heating the resulting mixture;
c) removing the solvent system;
d) adding a solvent selected from methyl tertiary butyl ether, acetonitrile, esters and mixtures thereof; and
e) isolating crystalline form A of fosamprenavir calcium.
4. The process according to claim 3 , wherein the solvent system in step a comprises acetonitrile, methanol, ethanol, butanol, acetone, water or mixtures thereof.
5. Crystalline fosamprenavir calcium form A according to claim 1 or 3 , characterized by a DSC thermogram as shown in FIG. 2 .
6. Crystalline fosamprenavir calcium form A according to claim 1 or 3 , characterized by a TGA thermogram as shown in FIG. 3 .
7. Crystalline fosamprenavir calcium form A according to claim 1 or 3 , characterized by an FT-IR spectra with characteristic absorption bands (cm −1 ) at 3467, 3373, 3062, 1690, 1317, 1147, 991, and 751.
8. Crystalline fosamprenavir calcium form A having a moisture content between 3 and 5.5 percent.
9. A process for the preparation of crystalline fosamprenavir calcium form A comprising the steps of:
a) suspending fosamprenavir calcium in a solvent system;
b) heating the resulting mixture;
c) removing the solvent system;
d) adding a solvent selected from methyl tertiary butyl ether, acetonitrile, ethyl acetate, acetone, water and mixtures thereof; and
e) isolating crystalline form A of fosamprenavir calcium.
10. The process according to claim 9 , wherein the solvent system in step a comprises acetonitrile, acetone, ethyl acetate, methanol, methyl tertiary butyl ether or mixtures thereof and the solvent in step d is selected from methyl tertiary butyl ether, acetonitrile, ethyl acetate, acetone, water and mixtures thereof.
11. A process for the preparation of crystalline fosamprenavir calcium form A comprising the steps of:
a) suspending fosamprenavir calcium in a solvent selected from acetonitrile, acetone, ethyl acetate, methanol and methyl tertiary butyl ether;
b) heating the resulting mixture;
c) optionally cooling the mixture;
d) optionally seeding the reaction mixture; and
e) isolating crystalline fosamprenavir calcium form A.
12. Crystalline fosamprenavir calcium form A according to claim 2 , characterized by a PXRD diffraction pattern having reflections at about 4.4°±0.2°, 5.0°±0.2°, 6.3°±0.2°, 7.4°±0.2° and 8.0°±0.2° 2 Θ.
13. Crystalline fosamprenavir calcium form A according to claim 12 , further characterized by additional reflections at about 3.3°±0.2°, 9.0°±0.2°, 9.8°±0.2°, 10.3°±0.2°, 11.5°±0.2°, and 12.1°±0.2° 2 Θ.