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

• Published in: Journal of drug delivery science and technology Vol. 53; p. 101132
• Main Authors: Hurley, Dean, Carter, David, Foong Ng, Lawrence Yee, Davis, Mark, Walker, Gavin M., Lyons, John G., Higginbotham, Clement L.
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 01.10.2019
• Subjects: Amorphous; Crystallization; Extrusion; Glass transition; Solid dispersion; Solubility; Glass transition; Amorphous; Solid dispersion; Extrusion; Crystallization; Solubility
• ISSN: 1773-2247
• DOI: 10.1016/j.jddst.2019.101132

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