Application of Dry Milling in the Preparation of Amorphous Ezetimibe/Polyvinylpyrrolidone-K30 Dispersions

Abstract

In the present study, polyvinylpyrrolidone-K30 along with dry milling approach was applied to improve the dissolution rate of ezetimibe, as a practically water-insoluble lipid lowering agent. The comilled formulations were prepared using different drug: polymer ratios and subjected to the milling process under different rotation speeds (100 & 400 rpm) and time durations (1 h & 3 h). The prepared samples were characterized before and after milling process. SEM results showed that the dry milling process considerably reduced the particle size to submicron ranges. Solid state analysis (DSC and PXRD) revealed that an increase in polymer ratio along with milling rotation speed resulted in the conversion of crystalline drug to an amorphous form. According to FTIR study, there was no detectable interaction between the drug and polymer during the process. The results denoted that the particle size reduction as well as drug amorphization during the co-milling process, provided remarkable improvement in dissolution performance of the prepared formulations.