Supercritical-CO₂ Foam Extrusion of Hydroxypropyl Methyl Cellulose Acetate Succinate/Itraconazole Amorphous Solid...

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 AFFINISOL^TM 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.