Application of dry milling in the preparation of amorphous ezetimibe/polyvinylpyrrolidone-K30 dispersions

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