Raltegravir salts and crystalline forms thereof
The present invention includes new salts of Raltegravir and crystalline forms thereof, pharmaceutical compositions containing the salts or crystalline forms, methods of using the salts or crystalline forms or the compositions to treat HIV infection or to prepare medicament for treating HIV infection, and a process for preparing Raltegravir potassium.
1. A crystalline form of Raltegravir potassium that is:
a) crystalline Form V of Raltegravir potassium, characterized by:
an X-ray powder diffraction pattern having peaks at 8.0, 11.9, 18.2 and 26.6 degrees two theta ±0.2 degrees two theta;
an X-ray powder diffraction pattern substantially as depicted in FIG. 2 ;
a solid-state 13 C NMR spectrum with signals at 121.9, 144.0, 149.3 and 170.3±0.2 ppm;
a solid-state 13 C NMR spectrum having chemical shifts differences between the signal exhibiting the lowest chemical shift and another in the chemical shift range of 100 to 180 ppm of 111.9, 134.0, 139.3 and 160.3±0.1 ppm;
a solid-state 13 C NMR spectrum substantially as depicted in FIG. 31 ; or combinations thereof; or
b) crystalline Form IV of Raltegravir potassium, characterized by:
an X-ray powder diffraction pattern having peaks at 6.5, 7.5, 8.1, 18.4 and 23.2 degrees two theta ±0.2 degrees two theta;
an X-ray powder diffraction pattern substantially as depicted in FIG. 1 ; or combinations thereof.
2. The crystalline Raltegravir potassium Form V according to claim 1 , characterized by:
an X-ray powder diffraction pattern having peaks at 8.0, 11.9, 18.2 and 26.6 degrees two theta ±0.2 degrees two theta;
an X-ray powder diffraction pattern substantially as depicted in FIG. 2 ;
a solid-state 13 C NMR spectrum with signals at 121.9, 144.0, 149.3 and 170.3±0.2 ppm;
a solid-state 13 C NMR spectrum having chemical shifts differences between the signal exhibiting the lowest chemical shift and another in the chemical shift range of 100 to 180 ppm of 111.9, 134.0, 139.3 and 160.3±0.1 ppm;
a solid-state 13 C NMR spectrum substantially as depicted in FIG. 31 ; or combinations thereof.
3. The crystalline Form V of Raltegravir potassium according to claim 2 ; characterized by an X-ray powder diffraction pattern having peaks at 8.0, 11.9, 18.2 and 26.6 degrees two theta ±0.2 degrees two theta.
4. The crystalline Form IV of Raltegravir potassium according to claim 1 , characterized by:
an X-ray powder diffraction pattern having peaks at 6.5, 7.5, 8.1, 18.4 and 23.2 degrees two theta ±0.2 degrees two theta;
an X-ray powder diffraction pattern substantially as depicted in FIG. 1 ; or combinations thereof.
5. The crystalline Raltegravir potassium Form IV according to claim 4 , characterized by
an X-ray powder diffraction pattern having peaks at 6.5, 7.5, 8.1, 18.4 and 23.2 degrees two theta ±0.2 degrees two theta, and further characterized by:
an X-ray powder diffraction pattern having additional peaks at 13.0, 17.5, 24.2 and 25.5 degrees two theta+0.2 degrees two theta;
a DSC thermogram as depicted in FIG. 27 ;
a TGA thermogram as depicted in FIG. 28 ;
or combinations thereof.
6. A pharmaceutical composition comprising the crystalline Form V or crystalline Form IV of Raltegravir potassium according to claim 1 , and at least one pharmaceutically acceptable excipient.
7. The crystalline Raltegravir potassium Form V according to claim 3 , further characterized by:
an X-ray powder diffraction pattern having additional peaks at 14.9, 19.8, 24.9, 27.7 and 28.9 degrees two theta ±0.2 degrees two theta;
a DSC thermogram substantially as depicted in FIG. 29 ;
a TGA thermogram substantially as depicted in FIG. 30 ;
an FT Raman spectrum substantially as depicted in FIG. 32 ; or combinations thereof.