Crystalline forms of tenofovir alafenamide
The present invention relates to novel crystalline forms of salts and/or co-crystals of tenofovir alafenamide, the pharmaceutical formulations, and the therapeutic uses thereof in treating viral infections.
1. Crystalline Tenofovir Alafenamide Sebacate Form I, characterized by an X-ray powder diffraction (XRPD) pattern having peaks at about 5.3°, 6.6°, 9.4°, 9.6°, and 19.8° 2-θ±0.2° 2-θ.
2. The crystalline form of claim 1 , wherein the X-ray powder diffraction (XRPD) pattern has further peaks at about 14.8°, 15.7°, 18.7°, 19.3°, and 22.1° 2-θ±0.2° 2-θ.
3. The crystalline form of claim 2 , wherein the X-ray powder diffraction (XRPD) pattern has further peaks at about 11.7°, 12.6°, 20.9°, 23.4°, 23.8°, 26.2°, 28.2°, and 29.0° 2-θ±0.2° 2-θ.
4. The crystalline form of claim 1 , characterized by an X-ray powder diffraction (XRPD) pattern as set forth in FIG. 5 .
5. The crystalline form of claim 1 , characterized by a differential scanning calorimetry (DSC) pattern as set forth in FIG. 6 .
6. A pharmaceutical composition comprising a therapeutically effective amount of the crystalline Tenofovir Alafenamide Sebacate of claim 1 and a pharmaceutically acceptable excipient.
7. The pharmaceutical composition of claim 6 , further comprising one to three additional therapeutic agents.
8. The pharmaceutical composition of claim 7 , wherein the additional therapeutic agents are each active against HIV.
9. The pharmaceutical composition of claim 6 , wherein the pharmaceutical composition is in a unit dosage form.
10. The pharmaceutical composition of claim 9 , wherein the unit dosage form is a subcutaneous injection.
11. The pharmaceutical composition of claim 9 , wherein the unit dosage form is an injection.
12. The pharmaceutical composition of claim 9 , wherein the unit dosage form is an intramuscular injection.
13. The pharmaceutical composition of claim 9 , wherein the crystalline Tenofovir Alafenamide Sebacate is in a suspension.
14. A method for treating a viral infection in a human, the method comprising administering to a human in need thereof a therapeutically effective amount of the crystalline Tenofovir Alafenamide Sebacate of claim 1 .
15. The method of claim 14 wherein the viral infection is caused by HIV.
16. The method of claim 14 , wherein the crystalline Tenofovir Alafenamide Sebacate is administered by injection.
17. The method of claim 14 , wherein the crystalline Tenofovir Alafenamide Sebacate is administered by intramuscular injection.
18. The method of claim 14 , wherein the crystalline Tenofovir Alafenamide Sebacate is administered by subcutaneous injection.
19. The method of claim 18 , wherein the crystalline Tenofovir Alafenamide Sebacate is in a suspension.
20. The method of claim 15 , wherein the crystalline Tenofovir Alafenamide Sebacate is in a long-acting formulation.
21. The method of claim 20 , wherein the long-acting formulation is active for at least 30 days.
22. The method of claim 21 , wherein the long-acting formulation maintains a concentration minimum (Cmin) above the efficacious level for HIV treatment.