Polymer/lipid interplay in altering in vitro supersaturation and plasma concentration of a model poorly soluble drug.,European Journal of Pharmaceutical Sciences

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Polymer/lipid interplay in altering in vitro supersaturation and plasma concentration of a model poorly soluble drug.
European Journal of Pharmaceutical Sciences ( IF 4.3 ) Pub Date : 2020-02-12 , DOI: 10.1016/j.ejps.2020.105262
Rui Peng ₁ , Jiahao Huang ₂ , Li He ₃ , Lina Zhao ₁ , Cuitong Wang ₁ , Wei Wei ₁ , Tongchao Xia ₁ , Yifei Mao ₁ , Yinghui Wen ₁ , Ling Wang ₁ , Junyi Yang ₁

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Supersaturation drug delivery system (SDDS) based on amorphous solid dispersion (ASD) is a widely used strategy to improve oral absorption of poorly water-soluble drugs by achieving a supersaturated state where drug concentration is significantly higher than drug solubility. However, dissolved drugs tend to recrystallize in gastrointestinal (GI) tract if without effective stabilizing excipients. In this paper, well-recognized polymer (polyvinylpyrrolidone, PVP) and lipid (phosphatidylcholine, PC) excipients are combined as ASD carrier, aiming at investigating the effects on evolution of in vitro supersaturation and in vivo plasma concentration of a model poorly soluble drug indomethacin (IND). Fundamental aspects including polymer/lipid composition ratio, drug loading (DL) degree and administration dose were investigated. The in vitro dissolution profiles of ASDs were assessed by supersaturation degree, duration, maximum achievable drug concentration and dose-normalized efficiency, and correlated with in vivo pharmacokinetic data. Results showed that both in vitro and in vivo concentration-time profiles of IND were significantly varying with abovementioned factors. Solution viscosity, solid-state properties and morphology of ASDs were related to the results. This study revealed fundamental mechanisms of PVP/PC mixture effect on IND supersaturation and oral bioavailability, demonstrating that polymer/lipid mixture could be used as a promising carrier to alter supersaturation profile and oral bioavailability of SDDS products.

中文翻译：

聚合物/脂质相互作用改变了模型难溶药物的体外过饱和度和血浆浓度。

基于无定形固体分散体（ASD）的过饱和药物输送系统（SDDS）是一种广泛使用的策略，可通过实现药物浓度明显高于药物溶解度的过饱和状态来改善水溶性差的药物的口服吸收。但是，如果没有有效的稳定赋形剂，溶解的药物往往会在胃肠道（GI）中重结晶。本文将公认的聚合物（聚乙烯吡咯烷酮，PVP）和脂质（磷脂酰胆碱，PC）赋形剂作为ASD载体，旨在研究难溶性药物吲哚美辛对体外过饱和和体内血浆浓度演变的影响。（IND）。研究了基本方面，包括聚合物/脂质组成比，药物载量（DL）程度和给药剂量。通过过饱和度，持续时间，可达到的最大药物浓度和剂量归一化效率评估了ASD的体外溶出度，并与体内药代动力学数据相关。结果表明，IND的体外和体内浓度-时间曲线均随上述因素而显着变化。ASD的溶液粘度，固态性质和形态与结果有关。这项研究揭示了PVP / PC混合物影响IND过饱和和口服生物利用度的基本机制，表明聚合物/脂质混合物可以用作改变SDDS产品过饱和曲线和口服生物利用度的有希望的载体。并与体内药代动力学数据相关。结果表明，IND的体外和体内浓度-时间曲线均随上述因素而显着变化。ASD的溶液粘度，固态性质和形态与结果有关。这项研究揭示了PVP / PC混合物影响IND过饱和和口服生物利用度的基本机制，表明聚合物/脂质混合物可以用作改变SDDS产品过饱和曲线和口服生物利用度的有希望的载体。并与体内药代动力学数据相关。结果表明，IND的体外和体内浓度-时间曲线均随上述因素而显着变化。ASD的溶液粘度，固态性质和形态与结果有关。这项研究揭示了PVP / PC混合物影响IND过饱和和口服生物利用度的基本机制，表明聚合物/脂质混合物可以用作改变SDDS产品过饱和曲线和口服生物利用度的有希望的载体。

更新日期：2020-02-12

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