Improving the Properties of Pharmaceutical Powders using Supercritical Anti-solvent Processing

Abstract

The effectiveness of a low-cost and easily scalable process co-milling (COM) was compared with the high-cost and precision-controlled supercritical anti-solvent (SAS) process to amorphize indomethacin (IDMC) with a water-soluble poly(vinylpyrrolidone) (PVP) polymer to improve the dissolution rate and physical stability of IDMC amorphous form. Different ratios of IDMC to PVP were generated using COM and SAS. The untreated, COM and SAS powders were characterized using SEM, X-ray-powder-diffractometry, thermogravimetric, gravimetric vapour sorption, FTIR, inverse gas chromatography and Raman mapping. Accelerated physical stability tests were evaluated on COM and SAS co-precipitates in open-pans at 75%RH/40deg.C. SAS co-precipitates with PVP contents more than 40wt.% were X-ray amorphous form and remained stable after more than 6-months of storage at 75%RH/40deg.C. COM powders with PVP contents less than 40wt.% re-crystallized after 7-days of storage at 75%RH/40deg.C. Amorphous form of IDMC generated by COM and SAS has improved dissolution properties as compared to the crystalline form.