Inhibition mechanism of hydroxypropyl methylcellulose acetate succinate on drug crystallization in gastrointestinal fluid and drug permeability from a supersaturated solution
Inhibition mechanism of hydroxypropyl methylcellulose acetate succinate on drug crystallization in gastrointestinal fluid and drug permeability from a supersaturated solution
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DOI：
10.1016/j.ejps.2014.06.007
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发表时间：
2014-10-01
影响因子：
4.6
通讯作者：
Moribe, Kunikazu
中科院分区：
文献类型：
--
作者：
Ueda, Keisuke;Higashi, Kenjirou;Moribe, Kunikazu
在药物结晶过程中评价胆汁酸/脂质胶束溶液中药物结晶抑制剂对药物渗透的影响。醋酸琥珀酸羟丙基甲基纤维素 (HPMC-AS) 被用作药物结晶抑制剂，在含有牛磺胆酸钠 (NaTC) 和蛋磷脂酰胆碱 (egg-PC) 的胃肠液模型中，可有效抑制地塞米松 (DEX) 结晶。使用质子核磁共振（H-1 NMR）实时监测DEX结晶过程中过饱和DEX分子状态的变化。结果表明，即使在 HPMC-AS 存在的情况下，在 DEX 结晶过程中，DEX 在本体水和由 NaTC 和 Egg-PC 形成的胶束相中的分布也没有改变。使用溶解/渗透率系统评估 DEX 结晶过程中的 DEX 渗透性。 HPMC-AS 的结晶抑制作用与 NaTC 和 Egg-PC 的胶束封装相结合，导致 DEX 浓度显着提高，并在 DEX 结晶过程开始时改善了 DEX 渗透性。即使在胶束溶液中，HPMC-AS 的结晶抑制也能有效发挥作用，其中 NaTC/egg-PC 胶束封装了一些 DEX。结论是结晶抑制剂有助于改善水溶性差的药物在胃肠液中的渗透。 (C) 2014 Elsevier B.V. 保留所有权利。
The effects of drug-crystallization inhibitor in bile acid/lipid micelles solution on drug permeation was evaluated during the drug crystallization process. Hydroxypropyl methylcellulose acetate succinate (HPMC-AS) was used as a drug-crystallization inhibitor, which efficiently suppressed dexamethasone (DEX) crystallization in a gastrointestinal fluid model containing sodium taurocholate (NaTC) and egg-phosphatidylcholine (egg-PC). Changes of molecular state of supersaturated DEX during the DEX crystallization process was monitored in real time using proton nuclear magnetic resonance (H-1 NMR). It revealed that DEX distribution to bulk water and micellar phases formed by NaTC and egg-PC was not changed during the DEX crystallization process even in the presence of HPMC-AS. DEX permeation during DEX crystallization was evaluated using dissolution/permeability system. The combination of crystallization inhibition by HPMC-AS and micellar encapsulation by NaTC and egg-PC led to considerably higher DEX concentrations and improvement of DEX permeation at the beginning of the DEX crystallization process. Crystallization inhibition by HPMC-AS can efficiently work even in the micellar solution, where NaTC/egg-PC micelles encapsulates some DEX. It was concluded that a crystallization inhibitor contributed to improvement of permeation of a poorly water-soluble drug in gastrointestinal fluid. (C) 2014 Elsevier B.V. All rights reserved.