An Insight into Stabilization Mechanism of a Solid Dispersion of Indomethacin/Partially Hydrolyzed Polyvinyl Alcohol Prepared by Hot-Melt Extrusion.

Abstract

We examined the effect of hot-melt extrusion condition on the physical stability of the solid dispersion prepared using partially hydrolyzed polyvinyl alcohol (PVOH). The hot-melt extrusion of indomethacin (IMC) and PVOH mixed at the weight ratio of 3 : 7, 5 : 5 and 7 : 3 was performed either at 170 or 190°C to prepare the IMC/PVOH hot-melt extrudate (HME). Differential scanning calorimetry represented that IMC was mixed with PVOH on a scale of several tens of nanometer in all the HMEs with different weight ratio. 13C solid-state NMR measurement revealed that an intermolecular interaction was formed between a carboxylic group of IMC and a hydroxy group of PVOH in the HMEs. The intermolecular interaction in the HMEs was stronger at the higher extrusion temperature. At the low IMC loading, the IMC molecules could be mixed with the amorphous PVOH at the molecular level, and the remained PVOH without interaction formed the crystal phase. On the other hand, at the high IMC loading, most PVOH could be amorphized by the interaction with IMC, and the excess IMC which did not interact with PVOH formed the IMC-rich domain. The IMC/PVOH HME at the weight ratio of 7 : 3 extruded at higher extrusion temperature showed higher physical stability of amorphous IMC compared with that extruded at lower extrusion temperature. The hot-melt extrusion process at higher temperature provided the rapid melting of PVOH crystal phase, resulted in the homogeneous mixing with IMC and the formation of stronger intermolecular interaction.