Impact of Hot-Melt Extrusion Processing Conditions on Physicochemical Properties of Amorphous Solid Dispersions Containing Thermally Labile Acrylic Copolymer

摘要: Abstract For successful formulation of amorphous solid dispersions (ASDs) using hot-melt extrusion, it is imperative to understand the effect that heat and shear rate has on physicochemical properties excipient. In this study, we investigated influence extrusion parameters solvent-free binary ASDs ibuprofen (IBU), a model active pharmaceutical ingredient, in methacrylic acid-ethyl acrylate copolymer type A, 1:1, EUDRAGIT® L100-55 (EUD). To evaluate impact barrel temperature, screw speed, residence time EUD mass average molar IBU release profile, size-exclusion chromatography dissolution testing were used, respectively. The optimal conditions established for loadings less than 40 wt. %. ASD formulations prepared ideal variables, spectral thermal analyses confirmed that, under dry at temperature 25°C, remained during an 18-month storage period. After 28 months, with ingredient content above 30 % started recrystallize. A temperature–composition phase diagram, constructed melting point depression glass-transition measurements IBU–EUD mixtures, correlated well long-term physical stability. minor-to-moderate polymer degradation within extrudates their stability characteristics analyzed discussed.