Bendamustine solid dispersions and continuous infusion

摘要

Provided herein are pharmaceutical compositions comprising nitrogen mustard, for example bendamustine hydrochloride, solid dispersions substantially free of degradants. Also provided are methods of producing and administering nitrogen mustards and in particular bendamustine hydrochloride solid dispersions substantially free of degradants. The pharmaceutical compositions can be used for any disease that is sensitive to treatment with bendamustine hydrochloride, such as neoplastic diseases.

主权项

1. A method for administering a dose of a nitrogen mustard compound to a patient comprising the steps of
a. contacting a stream of an intravenous infusion solution continuously flowing at a controlled rate with a stream of a second solution continuously flowing at a controlled rate and comprising the nitrogen mustard compound and either 1) polyvinylpyrrolidone and ethanol, or 2) mannitol and a solvent selected from the group consisting of dimethylsulfoxide, n-methyl-2-pyrrolidone, dimethylacetamide, polyethylene glycol, propylene glycol, glycerin, and mixtures thereof; b. mixing the solutions to provide a uniform and continuously flowing stream of a mixed solution which provides a pharmaceutical dose of 0.2 to 4.0 mg/ml of the nitrogen mustard compound; and c. administering the mixed solution to the patient, thereby administering the pharmaceutical dose of the nitrogen mustard compound to the patient, wherein the residence time period of the solutions from contacting to administering is 30, 20, 10, or 5 seconds or less.