Abiraterone prodrugs
Sustained-release abiraterone prodrug formulations, methods, and kits for parenteral administration to a subject having a sex hormone-dependent benign or malignant disorder such as prostate cancer, a syndrome due to androgen excess, and/or a syndrome due to glucocorticoid excess such as hypercortisolemia.
1. A crystalline form of a compound having the following formula,
wherein the crystalline form is characterized by an X-Ray Powder Diffraction (XRPD) spectrum having one or more of the following peaks: 4.6, 6.9, 8.7, 17.5, 18.3, 18.6, 19.1, 19.6, and 20.8, degrees 2 theta, ±0.2°.
2. The crystalline form of claim 1 , characterized by an XRPD spectrum having all of the following peaks: 4.6, 6.9, 8.7, 17.5, 18.3, 18.6, 19.1, 19.6, and 20.8, degrees 2 theta, ±0.2°.
3. The crystalline form of claim 1 , characterized by an XRPD spectrum substantially the same as shown in FIG. 12 A .
4. The crystalline form of claim 1 , further characterized by a Differential Scanning calorimetry (DSC) pattern having an endothermic peak with an onset temperature at about 69.0° C.
5. The crystalline form of claim 2 , further characterized by a Differential Scanning calorimetry (DSC) pattern having an endothermic peak with an onset temperature at about 69.0° C.
6. The crystalline form of claim 3 , further characterized by a Differential Scanning calorimetry (DSC) pattern having an endothermic peak with an onset temperature at about 69.0° C.
7. A substantially pure compound having the following formula,
characterized as having a purity by weight of greater than 95%.
8. The substantially pure compound of claim 7 , characterized as having a purity by weight of greater than 98%.
9. The substantially pure compound of claim 7 , characterized as having a purity by weight of greater than 99%.
10. The substantially pure compound of claim 7 , which is in a solid form.
11. The substantially pure compound of claim 10 , which is in a crystalline form characterized by an X-Ray Powder Diffraction (XRPD) spectrum having one or more of the following peaks: 4.6, 6.9, 8.7, 17.5, 18.3, 18.6, 19.1, 19.6, and 20.8, degrees 2 theta, =0.2°.
12. The substantially pure compound of claim 10 , which is in a crystalline form characterized by an X-Ray Powder Diffraction (XRPD) spectrum having all of the following peaks: 4.6, 6.9, 8.7, 17.5, 18.3, 18.6, 19.1, 19.6, and 20.8, degrees 2 theta, ±0.2°.
13. The substantially pure compound of claim 10 , which is in a crystalline form characterized by an XRPD spectrum substantially the same as shown in FIG. 12 A .
14. The substantially pure compound of claim 11 , wherein the crystalline form is further characterized by a Differential Scanning calorimetry (DSC) pattern having an endothermic peak with an onset temperature at about 69.0° C.
15. The substantially pure compound of claim 12 , wherein the crystalline form is further characterized by a Differential Scanning calorimetry (DSC) pattern having an endothermic peak with an onset temperature at about 69.0° C.
16. The substantially pure compound of claim 13 , wherein the crystalline form is further characterized by a Differential Scanning calorimetry (DSC) pattern having an endothermic peak with an onset temperature at about 69.0° C.
17. A salt of a compound having the following formula,
wherein the salt is an oxalate salt, a hydrochloride salt, a benzene sulfonate salt, a p-toluene sulfonate salt, or a phosphate salt.
18. A method of preparing a pharmaceutical composition suitable for parenteral administration to a subject having a sex hormone-dependent benign or malignant disorder, a syndrome due to androgen excess, and/or a syndrome due to glucocorticoid excess, comprising mixing the substantially pure compound of claim 7 with a pharmaceutically acceptable carrier.
19. A method of preparing a pharmaceutical composition suitable for parenteral administration to a subject having a sex hormone-dependent benign or malignant disorder, a syndrome due to androgen excess, and/or a syndrome due to glucocorticoid excess, comprising mixing the substantially pure compound of claim 8 with a pharmaceutically acceptable carrier.
20. A method of preparing a pharmaceutical composition suitable for parenteral administration to a subject having a sex hormone-dependent benign or malignant disorder, a syndrome due to androgen excess, and/or a syndrome due to glucocorticoid excess, comprising mixing the substantially pure compound of claim 9 with a pharmaceutically acceptable carrier.
21. A method of preparing a pharmaceutical composition suitable for parenteral administration to a subject having a sex hormone-dependent benign or malignant disorder, a syndrome due to androgen excess, and/or a syndrome due to glucocorticoid excess, comprising mixing the substantially pure compound of claim 10 with a pharmaceutically acceptable carrier.
22. A method of preparing a pharmaceutical composition suitable for parenteral administration to a subject having a sex hormone-dependent benign or malignant disorder, a syndrome due to androgen excess, and/or a syndrome due to glucocorticoid excess, comprising mixing the substantially pure compound of claim 11 with a pharmaceutically acceptable carrier.
23. A method of preparing a pharmaceutical composition suitable for parenteral administration to a subject having a sex hormone-dependent benign or malignant disorder, a syndrome due to androgen excess, and/or a syndrome due to glucocorticoid excess, comprising mixing the substantially pure compound of claim 12 with a pharmaceutically acceptable carrier.
24. A method of preparing a pharmaceutical composition suitable for parenteral administration to a subject having a sex hormone-dependent benign or malignant disorder, a syndrome due to androgen excess, and/or a syndrome due to glucocorticoid excess, comprising mixing the substantially pure compound of claim 13 with a pharmaceutically acceptable carrier.
25. The method of claim 18 , wherein the pharmaceutically acceptable carrier comprises a pharmaceutically acceptable oil and optionally a pharmaceutically acceptable solvent.
26. The method of claim 18 , wherein the pharmaceutically acceptable carrier comprises a pharmaceutically acceptable oil and a pharmaceutically acceptable solvent.
27. The method of claim 26 , wherein the pharmaceutically acceptable oil comprises a vegetable oil, castor oil, corn oil, sesame oil, cottonseed oil, peanut oil, poppy seed oil, tea seed oil, or soybean oil, the pharmaceutically acceptable solvent comprises benzyl alcohol and/or benzyl benzoate.
28. A pharmaceutical composition comprising the crystalline form of claim 1 .
29. A pharmaceutical composition comprising the crystalline form of claim 2 .
30. A pharmaceutical composition comprising the crystalline form of claim 3 .
31. The pharmaceutical composition prepared by the method of claim 18 .
32. The pharmaceutical composition prepared by the method of claim 25 .
33. The pharmaceutical composition prepared by the method of claim 26 .
34. The pharmaceutical composition prepared by the method of claim 27 .