期刊
JOURNAL OF PHARMACEUTICAL SCIENCES
卷 108, 期 9, 页码 3063-3073出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.xphs.2019.05.010
关键词
amorphous solid dispersion; ASD; melt extrusion; HPMCAS; surfactant; plasticization; viscosity; angular frequency; torque analysis; extrudability
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 degrees 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 degrees C, which is much lower than the minimum extrusion temperature of 170 degrees C for neat HPMCAS. (c) 2019 American Pharmacists Association (R). Published by Elsevier Inc. All rights reserved.
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