Dissolution enhancement of the anti-HIV drug UC 781 by formulation in a ternary solid dispersion with TPGS 1000 and Eudragit E100
Dissolution enhancement of the anti-HIV drug UC 781 by formulation in a ternary solid dispersion with TPGS 1000 and Eudragit E100
复制标题
DOI：
10.1016/j.ejpb.2008.07.006
复制
发表时间：
2008-11-01
影响因子：
4.9
通讯作者：
Van den Mooter, G.
中科院分区：
文献类型：
--
作者：
Goddeeris, C.;Willems, T.;Van den Mooter, G.
本研究涉及改善抗HIV药物UC 781的溶出特性。开发了由高量的TPGS 1000组成的三元固体分散体，其在流动性方面表现出良好的粉末性质。选择Eudragit E100作为聚合物基油过饱和研究。含有0至80%w/w药物剂量的固体分散体的DSC分析揭示了三元TPGS 100-Eudragit E100-UC 781混合物的共晶相行为。UC 781在模拟胃肠道腔的介质中的释放显着增强，4小时后达到70%w/w的释放。XRD结果表明，固体分散体中存在结晶药物。分散体中UC 781的存在对TPGS 1000-Eudragit E100载体具有全部影响，有利于TPGS 1000中聚乙二醇链的折叠。此外，向二元聚合物-表面活性剂混合物中添加UC 781在物理上表现为样品的流动性增加，直至载药量为50%w/w。NMR用于研究这种现象，揭示了载体对UC 781中的芳香族C原子和甲基的屏蔽和/或去屏蔽效应。TPGS 1000中存在的聚乙二醇链似乎在这一过程中发挥了作用。此外，将UC 781与TPGS 1000-Eudragit E100混合物组合导致出现玻璃化转变温度远低于纯化合物的Tg的TPGS 1000簇。(C)2008 Elsevier B. V.保留所有权利。
The present research deals with the improvement of the dissolution properties of the anti-HIV drug UC 781. A ternary solid dispersion consisting of a high amount of TPGS 1000 and exhibiting good powder properties with respect to flowability was developed. Eudragit E100 was selected as a polymer based oil supersaturation Studies. DSC analysis of solid dispersions containing drug doses from 0 to 80% w/w revealed eutectic phase behaviour of the ternary TPGS 100-Eudragit E100-UC 781 mixture. The release of UC 781 in a Medium Simulating the gastrointestinal lumen was markedly enhanced, reaching a release of 70% w/w after 4 h. XRD results pointed to the presence of crystalline drug ill the solid dispersion. The presence of UC 781 in the dispersion had all influence oil the TPGS 1000-Eudragit E100 carrier, favoring folding of the polyethylene glycol chains in TPGS 1000. Moreover, the addition of UC 781 to the binary polymer-surfactant mixture was physically expressed by all increase ill fluidity of the samples up to a drug load of 50% w/w. NMR was used to investigate this phenomenon, revealing a shielding and/or deshielding effect of the carrier on aromatic C atoms and methyl groups in UC 781. Polyethylene glycol chains present in TPGS 1000 seemed to play a role in this process. In addition, combining UC 781 with the TPGS 1000-Eudragit E100 mixture led to the appearance of TPGS 1000 clusters with a glass transition temperature well below the T-g's of the pure compounds. (C) 2008 Elsevier B.V. All rights reserved.