Processability of AquaSolve? LG polymer by hot-melt extrusion: Effects of pressurized CO_2 on physicomechanical properties and API stability

摘要

The objective of this study was to investigate the processability of AquaSolve? hydroxypropyl methylcellulose acetate succinate L grade (HPMCAS LG) via hot-melt extrusion and to examine the effect of pressurized carbon dioxide (P-CO_2) on the physicomechanical properties of efavirenz (EFA)-loaded extrudates. To optimize the process parameters and formulations, various physical mixtures of EFA (30%, 40%, and 50%, w/w) and HPMCAS LG (70%, 60%, and 50%, w/w), respectively, were extruded using a co-rotating twin-screw extruder with a standard screw configuration, with P-CO_2 injected into zone 8 of the extruder. Thermal characterization of the extrudates was performed using differential scanning calorimetry and thermogravimetric analysis. Scanning electron microscopy was employed to study the morphology and porosity of the formulations. Notably, the macroscopic morphology changed to a foam-like structure by P-CO_2 injection resulting in an increased specific surface area, porosity, and dissolution rate. Thus, HPMCAS LG extrusion, coupled with P-CO_2 injection, yielded faster dissolving extrudates. Stability studies indicated that HPMCAS LG was able to physically and chemically stabilize the amorphous state of high-dose EFA. Furthermore, the milling efficiency of the extrudates produced with P-CO_2 injection improved because of their increased porosity.