Institute of Physics, University of Silesia, ul. Uniwersytecka 4, 40-007 Katowice, Poland.
Mol Pharm. 2012 Apr 2;9(4):894-904. doi: 10.1021/mp200436q. Epub 2012 Mar 21.
In this paper, we present a novel way of stabilization of amorphous celecoxib (CEL) against recrystallization by preparing binary amorphous celecoxib-octaacetylmaltose (CEL-acMAL) systems by quench-cooling of the molten phase. As far as we know this is the first application of carbohydrate derivatives with acetate groups to enhance the stability of an amorphous drug. We found that CEL in the amorphous mixture with acMAL is characterized by a much better solubility than pure CEL. We report very promising results of the long-term measurements of stability of the CEL-acMAL binary amorphous system with small amount of stabilizer during its storage at room temperature. Moreover, we examined the effect of adding acMAL on molecular dynamics of CEL in the wide temperature range in both the supercooled liquid and glassy states. We found that the molecular mobility of the mixture of CEL with 10 wt % acMAL in the glassy state is much more limited than that in the case of pure CEL, which correlates with the better stability of the amorphous binary system. By dielectric measurements and theoretical calculations within the framework of density functional theory (DFT), we studied the role of acMAL in enhancing the stability of amorphous CEL in mixtures and postulated which interactions between CEL and acMAL molecules can be responsible for preventing devitrification.
本文提出了一种通过熔融相淬火冷却制备双无定形塞来昔布-辛烯基琥珀酸淀粉钠（CEL-acMAL）系统来稳定无定形塞来昔布（CEL）防止重结晶的新方法。据我们所知，这是首次将具有醋酸酯基团的碳水化合物衍生物应用于增强无定形药物稳定性。我们发现，无定形混合物中的 CEL 与 acMAL 相比具有更好的溶解度。我们报告了在室温下储存时，含有少量稳定剂的 CEL-acMAL 二元无定形系统的长期稳定性测量的非常有前景的结果。此外，我们在过冷液体和玻璃态的宽温度范围内研究了添加 acMAL 对 CEL 分子动力学的影响。我们发现，在玻璃态下，CEL 与 10wt%acMAL 的混合物的分子迁移率比纯 CEL 的分子迁移率受到更大的限制，这与无定形二元系统的更好稳定性相关。通过介电测量和密度泛函理论（DFT）框架内的理论计算，我们研究了 acMAL 在增强混合物中无定形 CEL 稳定性方面的作用，并假设 CEL 和 acMAL 分子之间的哪些相互作用可能有助于防止析晶。
