Effect of supercritical CO2 plasticization on the degradation and residual crystallinity of melt-extruded spironolactone

Immediate-release solid dispersions of a slowly dissolving active pharmaceutical ingredient, spironolactone, were prepared by supercritical-CO2-assisted melt extrusion (a solvent-free and continuous manufacturing technology) using Eudragit E as matrix. Through optimizing process parameters (i.e. temperature, melt throughput, pressure and CO2 flow), stable foams with high porosity, homogeneous structure and thin (even submicronic) walls could be prepared, as revealed by scanning electron microscopy. The samples were found to be rigid enough to mill, enabling further processing, as is necessary to formulate tablets. The influence of extrusion temperature and melt throughput on residual drug crystallinity was measured using non-invasive confocal Raman mapping coupled with chemometric analysis, while the influence on the degree of drug degradation was determined using high performance liquid chromatography. The plasticizing effect of supercritical CO2 was shown to reasonably improve the purity of the prepared solid dispersions by enabling high-yield production at lower temperature ranges. At the same time, shorter residence time and lower temperature slightly increased residual drug crystallinity. The obtained foamy structures ensured immediate drug dissolution in an acidic medium. Copyright (c) 2014 John Wiley & Sons, Ltd.