Details for Patent: 9,572,887

Title:	Formulations of bendamustine
Abstract:	Methods of treatment using bendamustine formulations designed for small volume intravenous administration are disclosed. The methods conveniently allow shorter administration time without the active ingredient coming out of solution as compared to presently available formulations.
Inventor(s):	Sundaram; Srikanth (Somerset, NJ)
Assignee:	EAGLE PHARMACEUTICALS, INC. (Woodcliff Lake, NJ)
Filing Date:	Jun 16, 2016
Application Number:	15/184,464
Claims:	1. A method of treating chronic lymphocytic leukemia or indolent B cell non-Hodgkin's lymphoma in a subject comprising: a. providing a non-aqueous liquid composition comprising from about 10 mg/mL to about 100 mg/mL of bendamustine or a pharmaceutically acceptable salt thereof, wherein the total impurities are less than about 5% as determined by HPLC at a wavelength of 223 nm after 15 months at a temperature of from about 5.degree. C. to about 25.degree. C.; b. diluting said non-aqueous liquid composition with a parenterally acceptable aqueous diluent; and c. parenterally administering said diluted composition to the subject at a bendamustine dosage ranging from about 25 mg/m.sup.2 to about 120 mg/m.sup.2, wherein said administering step is performed with a total volume of about 100 mL or less of the diluted composition administered over a period of less than or equal to about 15 minutes. 2. The method of claim 1, wherein the non-aqueous liquid composition comprises a pharmaceutically acceptable fluid comprising polyethylene glycol, propylene glycol, ethanol, benzyl alcohol, glycofurol, or DMSO, or a mixture thereof. 3. The method of claim 1, wherein the non-aqueous liquid composition comprises polyethylene glycol, propylene glycol, or a mixture thereof. 4. The method of claim 1, wherein the non-aqueous liquid composition comprises DMSO. 5. The method of claim 1, wherein the non-aqueous liquid composition comprises ethanol. 6. The method of claim 1, wherein the non-aqueous liquid composition comprises benzyl alcohol. 7. The method of claim 1, wherein the non-aqueous liquid composition comprises glycofurol. 8. The method of claim 1, wherein the subject is a human. 9. The method of claim 1, wherein the concentration of the bendamustine or pharmaceutically acceptable salt thereof in said diluted composition is from about 0.05 to about 12.5 mg/mL. 10. The method of claim 1, wherein the concentration of the bendamustine or pharmaceutically acceptable salt thereof in said diluted composition is from about 0.1 to about 6.0 mg/mL. 11. The method of claim 1, wherein the concentration of the bendamustine or pharmaceutically acceptable salt thereof in said diluted composition is from about 0.05 to about 3.2 mg/mL. 12. The method of claim 1, wherein the concentration of the bendamustine or pharmaceutically acceptable salt thereof in said diluted composition is from about 0.5 to about 5.6 mg/mL. 13. The method of claim 8, wherein the volume administered is about 50 mL. 14. The method of claim 1, wherein long term storage stable non-aqueous liquid composition further comprises a stabilizing amount of an antioxidant. 15. The method of claim 14, wherein the antioxidant is selected from the group consisting of thioglycerol, monothioglycerol, lipoic acid, propyl gallate, methionine, cysteine, metabisulfites, sodium formaldehyde sulfoxylate, phenol-containing aromatic and aliphatic compounds and dihydrolipoic acid. 16. The method of claim 1, wherein the subject is being treated for chronic lymphocytic leukemia. 17. The method of claim 16, wherein the diluted composition is administered intravenously in a volume of about 50 mL in about 10 minutes or less on days 1 and 2 of a 28 day cycle. 18. The method of claim 17, wherein the diluted composition is administered in about 10 minutes. 19. The method of claim 17, wherein the method is repeated for up to 6 cycles. 20. The method of claim 16, wherein the subject is administered a bendamustine dosage amount ranging from about 25 mg/m.sup.2 to about 100 mg/m.sup.2. 21. The method of claim 20, wherein the bendamustine dosage amount is about 100 mg/m.sup.2. 22. The method of claim 16, wherein the diluted composition comprises from about 1.85 mg/mL to about 4.84 mg/mL of bendamustine or a pharmaceutically acceptable salt thereof. 23. The method of claim 1, wherein the bendamustine is administered to treat indolent B cell non-Hodgkin's lymphoma. 24. The method of claim 23, wherein the diluted composition is administered intravenously in a volume of about 50 mL in about 10 minutes or less on days 1 and 2 of a 21 day cycle. 25. The method of claim 24, wherein the diluted composition is administered in about 10 minutes. 26. The method of claim 24, wherein the method is repeated for up to 8 cycles. 27. The method of claim 23, wherein the subject is administered a bendamustine dosage amount ranging from about 60 mg/m.sup.2 to about 120 mg/m.sup.2. 28. The method of claim 23, wherein the subject is administered a bendamustine dosage amount of about 120 mg/m.sup.2. 29. The method of claim 28, wherein the diluted liquid composition comprises from about 2.19 mg/mL to about 5.59 mg/mL of bendamustine or a pharmaceutically acceptable salt thereof.