Effects of Surfactants on Itraconazole-Hydroxypropyl Methylcellulose Acetate Succinate Solid Dispersion Prepared by Hot Melt Extrusion. II: Rheological Analysis and Extrudability Testing.
Although hydroxypropyl methylcellulose acetate succinate (HPMCAS) has been widely used as a carrier for amorphous solid dispersion of poorly water-soluble drugs, its application has mostly been limited to spray drying, and the solvent-free method of hot melt extrusion has rarely been used. This is on account of the high temperature (≥170°C) required for extrusion where the polymer and even a drug may degrade. In part 1 of this series of papers, we demonstrated that HPMCAS is miscible with surfactants such as, poloxamer 188, poloxamer 407 and d-alpha tocopheryl polyethylene glycol 1000 succinate, which may also serve as plasticizers (Solanki et al., J Pharm Sci. 2019; 108 (4):1453-1465). The present investigation was undertaken to determine plasticization effects of the surfactants and a model drug, itraconazole, in reducing melt extrusion temperatures of HPMCAS. The determination of complex viscosity as functions of temperature and also as functions of angular frequency at certain fixed temperatures showed that the surfactants and the drug greatly reduce viscosity of HPMCAS by their plasticization effects. Surfactants and drug also had synergistic effects in reducing viscosity. The torque analysis during melt extrusion demonstrated that these additives greatly enhanced extrudability of HPMCAS. Surfactant-drug-polymer mixtures were successfully extruded as stable amorphous solid dispersions at 130°C, which is much lower than the minimum extrusion temperature of 170°C for neat HPMCAS.
['Solanki|Nayan G|NG|', 'Gumaste|Suhas G|SG|', 'Shah|Ankita V|AV|', 'Serajuddin|Abu T M|ATM|']
D002152:Calorimetry, Differential Scanning D004337:Drug Carriers D004339:Drug Compounding D000080048:Hot Melt Extrusion Technology D006358:Hot Temperature D006863:Hydrogen-Ion Concentration D017964:Itraconazole D008747:Methylcellulose D012212:Rheology D013501:Surface-Active Agents D014783:Viscosity
surfactant melt extrusion extrudability HPMCAS amorphous solid dispersion plasticization viscosity angular frequency torque analysis ASD