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. A crystalline form of Tenofovir Alafenamide Hemipamoate, wherein the crystalline form is crystalline Tenofovir Alafenamide Hemipamoate Form I, characterized by an X-ray powder diffraction (XRPD) pattern having peaks at about 7.4°, 8.4°, 10.6°, 14.8°, and 22.3°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 17.4°, 19.0°, 20.1°, 23.8°, and 25.7° 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 11.2°, 13.1°, 13.8°, 15.8°, 21.0°, and 28.8° 2-θ±0.2° 2-θ.
4. The crystalline form of claim 1 , characterized by an X-ray powder diffraction (XRPD) pattern substantially as set forth in FIG. 1 .
5. The crystalline form of claim 1 , characterized by differential scanning calorimetry (DSC) pattern substantially as set forth in FIG. 2 .
6. A pharmaceutical composition comprising a therapeutically effective amount of the crystalline Tenofovir Alafenamide Hemipamoate Form I 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. A method for treating a virus infection in a human, the method comprising administering to a human in need thereof a therapeutically effective amount of the crystalline Tenofovir Alafenamide Hemipamoate Form I of claim 1 .
12. The method for treating a virus infection in a human of claim 11 , wherein the virus infection is caused by HIV.
13. The pharmaceutical composition of claim 9 , wherein the unit dosage form is an injection.
14. The pharmaceutical composition of claim 9 , wherein the unit dosage form is an intramuscular injection.
15. The pharmaceutical composition of claim 9 , wherein the crystalline Tenofovir Alafenamide Hemipamoate Form I is in a suspension.
16. The method of claim 11 , wherein the crystalline Tenofovir Alafenamide Hemipamoate Form I is administered by injection.
17. The method of claim 11 , wherein the crystalline Tenofovir Alafenamide Hemipamoate Form I is administered by intramuscular injection.
18. The method of claim 11 , wherein the crystalline Tenofovir Alafenamide Hemipamoate Form I is administered by subcutaneous injection.
19. The method of claim 18 , wherein the crystalline Tenofovir Alafenamide Hemipamoate Form I is in a suspension.
20. The method of claim 12 , wherein the crystalline Tenofovir Alafenamide Hemipamoate Form I 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.