Effects of Surfactants on Itraconazole-Hydroxypropyl Methylcellulose Acetate Succinate Solid Dispersion Prepared by Hot Melt Extrusion. II: Rheological Analysis and Extrudability Testing

摘要: Abstract Although hydroxypropyl methylcellulose acetate succinate (HPMCAS) has been widely used as a carrier for amorphous solid dispersion of poorly water-soluble drugs, its application mostly limited to spray drying, and the solvent-free method hot melt extrusion rarely used. This is on account high temperature (≥170°C) required where polymer even drug may degrade. In part 1 this series papers, we demonstrated that HPMCAS miscible with surfactants such as, poloxamer 188, 407 d-alpha tocopheryl polyethylene glycol 1000 succinate, which also serve plasticizers (Solanki et al., J Pharm Sci. 2019; 108 (4):1453-1465). The present investigation was undertaken determine plasticization effects model drug, itraconazole, in reducing temperatures HPMCAS. determination complex viscosity functions angular frequency at certain fixed showed greatly reduce by their effects. Surfactants had synergistic viscosity. torque analysis during these additives enhanced extrudability Surfactant-drug-polymer mixtures were successfully extruded stable dispersions 130°C, much lower than minimum 170°C neat