Solid forms of bendamustine hydrochloride
Novel solid forms of bendamustine hydrochloride are described, as well as methods of their preparation and use.
1. A crystalline form of bendamustine hydrochloride that is bendamustine hydrochloride Form 3, that produces an X-ray powder diffraction pattern comprising the following reflections: 7.9, 15.5, and 26.1±0.2 degrees 2θ.
2. The bendamustine hydrochloride according to claim 1 that produces an X-ray powder diffraction pattern further comprising one or more of the following reflections: 10.6, 19.7 and/or 23.3±0.2 degrees 2θ.
3. The bendamustine hydrochloride according to claim 1 that is substantially free of other crystalline forms of bendamustine hydrochloride.
4. A composition comprising the crystalline form of bendamustine hydrochloride according to claim 1 .
5. The composition according to claim 4 , further comprising at least one pharmaceutically acceptable excipient.
6. The composition according to claim 4 , wherein the composition is substantially free of other crystalline forms of bendamustine hydrochloride.
7. The composition according to claim 5 , wherein the composition is substantially free of other crystalline forms of bendamustine hydrochloride.
8. The composition according to claim 4 , wherein the composition further comprises amorphous bendamustine hydrochloride.
9. The composition according to claim 5 , wherein the composition further comprises amorphous bendamustine hydrochloride.
10. The composition according claim 4 , wherein the pharmaceutically acceptable excipient is sodium phosphate, potassium phosphate, citric acid, tartaric acid, gelatin, glycine, mannitol, lactose, sucrose, maltose, glycerin, dextrose, dextran, trehalose, hetastarch, or a mixture thereof.
11. The composition according to claim 10 wherein the excipient is mannitol.
12. The composition according to claim 4 wherein the composition is a pharmaceutical composition.
13. A lyophilized composition comprising the crystalline form of bendamustine hydrochloride according to claim 1 , at least one pharmaceutically acceptable excipient, and an organic solvent.
14. The lyophilized composition of claim 13 , wherein the lyophilized composition further comprises amorphous bendamustine hydrochloride.
15. The lyophilized composition of claim 13 , wherein the lyophilized composition is substantially free of other crystalline forms of bendamustine hydrochloride.
16. The lyophilized composition of claim 13 , wherein the pharmaceutically acceptable excipient is sodium phosphate, potassium phosphate, citric acid, tartaric acid, gelatin, glycine, mannitol, lactose, sucrose, maltose, glycerin, dextrose, dextran, trehalose, hetastarch, or a mixture thereof.
17. The lyophilized composition of claim 16 , wherein the excipient is mannitol.
18. The lyophilized composition of claim 13 , wherein the organic solvent is methanol, ethanol, n-propanol, iso-propanol, n-butanol, tert-butanol, or mixtures thereof.
19. The lyophilized composition of claim 18 , wherein the organic solvent is tert-butanol.
20. The lyophilized composition of claim 19 , further comprising amorphous bendamustine hydrochloride and mannitol.
21. A method of treating chronic lymphocytic leukemia, Hodgkin's disease, non-Hodgkin's lymphoma, multiple myeloma or breast cancer in a patient in need thereof comprising administering to the patient a composition comprising the crystalline form of bendamustine hydrochloride according to claim 1 .
22. The method according to claim 21 , wherein the non-Hodgkin's lymphoma is indolent B-cell non-Hodgkin's lymphoma.