A new twist in the old story-can compression induce mixing of phase separated solid dispersions? A case study of spray-dried miconazole-PVP VA64 solid dispersions.

Abstract

The phase response of Miconazole-PVP VA64 solid dispersions upon compression was investigated. This would allow understanding the phase behavior of these solid dispersions upon application of a different kind of stress (other than humidity and temperature) and ultimately lead to mechanistic perception of the phase changes taking place. Miconazole and PVP VA64 were chosen as a model drug and polymer, respectively and solid dispersions were prepared by spray drying. Dried solid dispersions were compressed using different compression pressure but constant dwell time. MDSC and XRPD were used to characterize and study the effect of compression on the system. The solid dispersions showed a single Tg till 20% drug loading after which two Tg's were observed. Application of compression to the phase separated 30 and 40% compositions induced mixing resulting in only a single Tg. This reduction in number of Tg's upon compression is a result of mixing which can be attributed to polymer flow resulting in reduction of the domain size of different phases in the solid dispersions. Application of compression can influence the phase behavior of Miconazole-PVP VA64 solid dispersions. This observation may have drastic impact on the formulation development approach for solid dispersions to be administered as tablets.