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Abstract：
In this study, an amorphous solid dispersion containing the poorly water-soluble drug, bisacodyl, was prepared by hot-melt extrusion to enhance its therapeutic efficacy. First, the miscibility and interaction between the drug and polymer were investigated as pre-formulation strategies using various analytical approaches to obtain information for selecting a suitable polymer. Based on the calculation of the Hansen solubility parameter and the identification of the single glass transition temperature (Tg), the miscibility between bisacodyl and all the investigated polymers was confirmed. Additionally, the drug-polymer molecular interaction was identified based on the comprehensive results of dynamic vapor sorption (DVS), Fourier transform infrared spectroscopy (FT-IR), Raman spectroscopy, and a comparison of the predicted and experimental values of Tg. In particular, the hydroxypropyl methylcellulose (HPMC)-based solid dispersions, which exhibited large deviation between the calculated and experimental values of Tg and superior physical stability after DVS experiments, were selected as the most appropriate solubilized bisacodyl formulations due to the excellent inhibitory effects on precipitation based on the results of the non-sink dissolution test. Furthermore, it was shown that the enteric-coated tablets containing HPMC-bisacodyl at a 1:4 ratio (w/w) had significantly improved in vivo therapeutic laxative efficacy compared to preparations containing un-solubilized raw bisacodyl in constipation-induced rabbits. Therefore, it was concluded that the pre-formulation strategy, using several analyses and approaches, was successfully applied in this study to investigate the miscibility and interaction of drug-polymer systems, hence resulting in the manufacture of favorable solid dispersions with favorable in vitro and in vivo performances using hot-melt extrusion processes.
摘要：
在这项研究中,含有水溶性差的药物的无定形固体分散体，比沙科迪尔,通过热熔挤出制备以增强其治疗效果。首先,药物与聚合物之间的混溶性和相互作用作为预配制策略进行了研究,使用各种分析方法来获得选择合适聚合物的信息.基于Hansen溶解度参数的计算和单一玻璃化转变温度（Tg）的确定，bisacodyl和所有研究的聚合物之间的混溶性被证实。此外,基于动态蒸气吸附(DVS)的综合结果鉴定了药物-聚合物分子相互作用，傅里叶变换红外光谱(FT-IR),拉曼光谱,并比较了Tg的预测值和实验值。特别是,基于羟丙基甲基纤维素（HPMC）的固体分散体，在DVS实验后，Tg的计算值与实验值之间存在较大偏差，并且具有出色的物理稳定性，由于基于非汇溶出测试的结果对沉淀具有优异的抑制作用,因此被选择为最合适的溶解的比沙可啶制剂。此外，研究表明，与含有未溶解的生比沙可啶的制剂相比，含有1:4比例（w/w）的HPMC-比沙可啶的肠溶片在便秘诱导的兔子中的体内治疗性泻药功效显着提高。因此,得出的结论是，制定前的战略，使用几种分析和方法，在这项研究中成功地应用于研究药物-聚合物系统的混溶性和相互作用，因此导致使用热熔挤出方法制造具有有利的体外和体内性能的有利的固体分散体。
