COMPLEXATION METHODS WITH CYCLODEXTRINS FOR THE INTRODUCTION OF PEPTIDE PROTEASOMIC INHIBITORS INTO PHARMACEUTICAL COMPOSITIONS

摘要

The invention relates to methods for formulating compositions containing one or more peptide proteasome inhibitors and cyclodextrin, in particular substituted cyclodextrin, as well as methods for complexing with cyclodextrins in preparing the composition of the peptide proteasome inhibitor (for example, compounds of formulas (1) to (5) or its pharmaceutical acceptable salt) with one or more cyclodextrins. Such methods significantly increase the solubility and stability of these proteasome inhibitors and facilitate both their manufacture and their administration. For example, homogeneous solutions of the compound of formula (5) (carfilzomib) can be obtained at a pharmaceutically acceptable pH (eg, about 3.5) and at higher concentrations (eg, about 5 mg / ml) than could be obtained without one or several cyclodextrins and methods of complexation between the compound and one or more cyclodextrins presented in this document.