Effects of Surfactants on Itraconazole-Hydroxypropyl Methylcellulose Acetate Succinate Solid Dispersion Prepared by Hot Melt Extrusion. II: Rheological Analysis and Extrudability Testing
Effects of Surfactants on Itraconazole-Hydroxypropyl Methylcellulose Acetate Succinate Solid Dispersion Prepared by Hot Melt Extrusion. II: Rheological Analysis and Extrudability Testing
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DOI：
10.1016/j.xphs.2019.05.010
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发表时间：
2019-09-01
影响因子：
3.8
通讯作者：
Serajuddin, Abu T. M.
中科院分区：
文献类型：
--
作者：
Solanki, Nayan G.;Gumaste, Suhas G.;Serajuddin, Abu T. M.
虽然羟丙基甲基纤维素乙酸琥珀酸酯（HPMCAS）作为非晶态固体分散剂已被广泛应用于难水溶性药物的载体，但其应用大多局限于喷雾干燥，热熔挤压的无溶剂方法很少使用。这是由于挤出所需的高温（>= 170℃），聚合物甚至药物都可能降解。在本系列论文的第1部分，我们证明了HPMCAS与poloxam188、poloxam407和d- α生育酚基聚乙二醇1000琥珀酸盐等表面活性剂可混溶，这些表面活性剂也可作为增塑剂（Solanki et al., J Pharm Sci. 2019; 108(4):1453-1465）。本研究确定了表面活性剂和模型药物伊曲康唑对降低HPMCAS熔体挤出温度的塑化作用。在一定的固定温度下，复合粘度随温度和角频率的函数的测定表明，表面活性剂和药物通过其塑化作用大大降低了HPMCAS的粘度。表面活性剂和药物在降低黏度方面也有协同作用。熔体挤出过程中的扭矩分析表明，这些添加剂显著提高了HPMCAS的挤出性能。表面活性剂-药物-聚合物混合物在130℃下成功挤压成稳定的非晶态固体分散体，远低于纯HPMCAS的最低挤压温度170℃。(c) 2019年美国药剂师协会(R)。Elsevier Inc.出版。版权所有。
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.