The effect of PEG molecular weights on the thermal stability and dissolution behaviors of griseofulvin-PEG crystalline inclusion complexes
The effect of PEG molecular weights on the thermal stability and dissolution behaviors of griseofulvin-PEG crystalline inclusion complexes
复制标题
PEG分子量对灰黄霉素-PEG结晶包合物热稳定性和溶解行为的影响
DOI：
10.1016/j.ijpharm.2016.05.014
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发表时间：
2016-07-11
影响因子：
5.8
通讯作者：
Huang, Yanbin
中科院分区：
文献类型：
--
作者：
Yang, Xiaotong;Zhong, Zhi;Huang, Yanbin
小分子药物和亲水性共形成物之间形成的共晶体已经显示出优化药物物质的溶出曲线的巨大潜力。到目前为止，大多数使用的共形成物是小分子。然而，线性聚合物也能够形成药物-聚合物结晶包合复合物（IC）。与小分子共形成物相比，聚合物共形成物的分子量可以容易地改变而不破坏IC晶体结构，因此代表了一种有趣的调节IC性质的方法。在这项研究中，我们研究了PEG分子量对Gris-PEG IC的热稳定性和溶解行为的影响。结果表明，随着PEG分子量的增加，Gris-PEG IC晶体的热稳定性先增加，然后达到一个平台值，同时存在一个最佳的PEG分子量。实验结果解释了两种类型的晶体缺陷的形成过程中的IC在PEG熔体中生长：空洞缺陷和晶界缺陷。这是首次对药物-聚合物结晶包合物的药物特性进行研究。(C)© 2016 Elsevier B. V.版权所有。
Co-crystals formed between small molecular drugs and hydrophilic co-formers have shown great potential to optimize the dissolution profiles of drug substances. So far most of the co-formers used are small molecules. However, linear polymers are also able to form drug-polymer crystalline inclusion complexes ( ICs). In contrast to the small molecular co-formers, molecular weight of the polymer co-formers can be easily changed without disrupting the IC crystal structure, and hence represents an interesting approach to tune the IC properties. In this study, we investigated the effect of PEG molecular weights on the thermal stability and dissolution behavior of Gris-PEG ICs. It was found that the thermal stability of Gris-PEG IC crystals first increased with PEG molecular weight, and then reached a plateau value, while an optimized PEG molecular weight existed for the dissolution profile. The experimental results were explained by the formation of two types of crystal defects during the IC growth in PEG melt: the void defects and the grain boundary defects. This is the first study on the pharmaceutical profiles of drug-polymer crystalline inclusion complexes. (C) 2016 Elsevier B.V. All rights reserved.