A Comparison of the Crystallization Inhibition Properties of Bile Salts
A Comparison of the Crystallization Inhibition Properties of Bile Salts
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DOI：
10.1021/acs.cgd.6b01470
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发表时间：
2016-12-01
影响因子：
3.8
通讯作者：
Taylor, Lynne S.
中科院分区：
文献类型：
--
作者：
Li, Na;Mosquera-Giraldo, Laura I.;Taylor, Lynne S.
胆盐是存在于人胃肠道中的天然表面活性剂。因此，必须考虑它们对口服药物制剂的溶出和结晶倾向的影响。虽然最近的一项研究表明，牛磺胆酸钠延迟成核的11种结构不同的化合物，有有限的信息，其他胆汁盐的结晶抑制性能，以及它们是否可以互换在这种情况下。在这项研究中，我们评估了13种胆汁盐维持三种化合物（塞来昔布、奈韦拉平和非班色林）过饱和水溶液的能力。大多数胆汁盐延长成核诱导时间。然而，它们的抑制作用根据胆汁盐和药物的结构和浓度而变化。胆汁盐的R5基团和疏水性似乎是必不可少的。分子动力学模拟结果表明奈韦拉平与胆盐之间存在货车范德华力和氢键相互作用，但在不同体系中存在差异。这些结果对于更好地理解口服递送的水溶性差的化合物在体内的结晶倾向是重要的。
Bile salts are natural surfactants present in the human gastrointestinal tract. Therefore, it is essential to consider their effect on the dissolution and crystallization tendency of oral drug formulations. Although a recent study showed that sodium taurocholate delayed nucleation for 11 structurally diverse compounds, there is limited information about the crystallization inhibition properties of other bile salts and whether they are interchangeable in this context. In this study, we evaluated the ability of 13 bile salts to maintain supersaturated aqueous solutions of three compounds: celecoxib, nevirapine, and fibanserin. Most bile salts extended nucleation induction times. However, their inhibitory effects varied depending on the structure and concentration of the bile salt and the drug. The R5 group and hydrophobicity of the bile salt appeared to be essential. Molecular dynamics simulations indicated that van der Waals and hydrogen bonding interactions occurred between nevirapine and bile salts, with variations in different systems. These results are important to better understand the crystallization tendency of orally delivered poorly water-soluble compounds in vivo.