Supercritical-CO2 Foam Extrusion of Hydroxypropyl Methyl Cellulose Acetate Succinate/Itraconazole Amorphous Solid Dispersions: Processing-Structure-Property Relations.

Abstract

This study investigates the effects of supercritical CO2 as a foaming agent on structure and physical properties of hot melt extruded hydroxypropyl methylcellulose acetate succinate (HPMCAS)-itraconazole (ITZ) amorphous solid dispersions (ASDs) with the aim of improving the milling efficiency and tabletability of these ASDs. Two different grades of AFFINISOLTM HPMCAS, the standard grade (Std) and the High Productivity grade (HP) were used. The HP-grade has a lower molecular weight, melt viscosity and wider processing temperature range. Extrudates with different ITZ concentrations (0%, 20% and 40%) and CO2 injection pressure of 100 and 200 bar were prepared. The cellular microstructure of the foams showed that HP-grade HPMCAS had better affinity with the CO2 resulting in better distribution of CO2. The results of DSC and X-ray diffraction analysis revealed that the supercritical CO2 did not affect the amorphous state of the API in the extrudates. Milling efficiency of the ASDs was significantly improved up to around 90% increase in the mass recovery. The tabletability of the milled extrudates showed a considerable increase in tablet tensile strength. In addition, foaming considerably improved the supersaturation of HP-grade ASD while showing minimal improvement in dissolution behavior of the Std-grade material.