How changes in molecular weight and PDI of a polymer in amorphous solid dispersions impact dissolution performance

This study evaluated the impact of HME process conditions on physical characteristics of poly(vinylpyrrolidone-co-vinyl-acetate) 60:40 (PVP-VA64) which is a widely used polymer for HME. Focus was set on molecular weight (Mw) and polydispersity index (PDI), by means of absolute molar mass detection via multi-angle light scattering. The generation of a high Mw fraction together with a decrease of the average Mw was detected. In a next step, the influence of these changes on the dissolution behavior of ASD was evaluated. Different stress conditions were applied onto PVP-VA64 in placebo extrusions. The obtained stressed polymer samples were subsequently used to prepare verum ASD with ketoconazole by spray drying (SD). SD dispersions (SDD) of thermally stressed PVP-VA64 were compared to SDD prepared with bulk powder. Although there were only slight changes in Mw and PDI, they significantly impacted supersaturation and precipitation of the formulation.Graphical abstract
Source: International Journal of Pharmaceutics - Category: Drugs & Pharmacology Source Type: research