An investigation of the inter-molecular interaction, solid-state properties and dissolution properties of mixed Copovidone hot-melt extruded solid dispersions.

Abstract

Previous research has focused on spray dried quaternary mixtures which due to the addition of a surfactant 26 affected the physical stability and amorphous stability of selected model drugs. Very little research has 27 focused on how inter-molecular interactions play a role in the successful formulation of hot-melt extruded 28 quaternary amorphous blends and how they affect physical stability and solubility of amorphous solid 29 dispersions (ASDs). Therefore the aim of this study was to investigate the role of inter-molecular 30 interactions and their effect on the solid-state and dissolution properties of mixed copovidone amorphous 31 solid dispersions (ASDs). The polymeric copovidone carriers used in this study was Poly (vinylpyrrolidone-32 vinyl acetate copolymer) and Plasdone S-630 (PL-S630) which in terms of monographs are the same, 33 however they have different solid-state and dissolution properties. The ASDs showed a significantly higher 34 dissolution rate compared to amorphous and pure INM in pH buffer 1.2 with a kinetic solubility of 24 35 μg/ml. The stability data showed that INM remained amorphous in solid solutions with PVP VA64 and 36 Plasdone S-630, except for the higher drug loads. It was concluded that % drug loading did have a 37 significant effect on the solubility of INM due to recrystallization at higher drug loads.