Understanding the Processing Window of Hypromellose Acetate Succinate for Hot-Melt Extrusion, Part I: Polymer Characterization and Hot-Melt Extrusion

The aims of this study were to assess the processing window of hypromellose acetate succinate (HPMCAS) as a polymeric carrier for hot-melt extrusion, and to investigate the effect of screw configuration and processing parameters on the physicochemical properties of HPMCAS extrudates. The processability was investigated using a Brabender (R) mixer and a Pharma 11 Twin Screw Extruder. HPMCAS extrudates were characterized with regard to glass transition temperature, true density, yellowness index, crystallinity, morphology, and free succinic acid/acetic acid/succinoyl group/acetyl group content. The specific energy input and mean residence time were also calculated and correlated to the physicochemical properties of final extrudates. Additionally, the effect of the die opening size of the twin screw extruder was investigated. The glass transition temperature of HPMCAS was found to be 137 and 133 degrees C, using dynamic mechanical analyzer and oscillatory rheometer, respectively. HPMCAS demonstrated a shear thinning behavior at all temperatures tested (150, 160, and 170 degrees C). The process conditions, screw configurations, as well as the diameter of die opening significantly affect the amount of free acetic acid and succinic acid. With a modified screw configuration and 1-mm die, the amounts of free acetic acid and succinic acid from the material processed at 180 degrees C were 0.114% and 0.337%, respectively. Moreover, when the die was removed, the amounts of free acetic acid and succinic acid were further reduced to 0.084% and 0.294%, respectively. In conclusion, we successfully extruded HPMCAS at a temperature as low as 130 degrees C and up to 180 degrees C without any significant thermal degradation.