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影响作为疏水性药物口服控释基质的有机凝胶的侵蚀速率和药物释放动力学的因素。

Factors influencing the erosion rate and the drug release kinetics from organogels designed as matrices for oral controlled release of a hydrophobic drug.

作者信息

Pereira Camelo Sarah Regina, Franceschi Sophie, Perez Emile, Girod Fullana Sophie, Ré Maria Inês

机构信息

a Mines Albi, CNRS, Centre RAPSODEE, Campus Jarlard, Université De Toulouse , Albi CT Cedex , France .

b Laboratoire Des I.M.R.C.P. , Université Paul Sabatier , Toulouse , France , and.

出版信息

Drug Dev Ind Pharm. 2016;42(6):985-97. doi: 10.3109/03639045.2015.1103746. Epub 2015 Nov 7.

Abstract

This article proposes solid-like systems from sunflower oil structured with a fibrillar network built by the assembly of 12-hydroxystearic acid (12-HSA), a gelator molecule for an oil phase. The resulting organogels were studied as oral controlled release formulations for a lipophilic drug, Efavirenz (EFV), dissolved in the oil. The effects of the gelator concentration on the thermal properties of the organogels were studied by Differential Scanning Calorimetry (DSC) and showed that drug incorporation did not change the sol-gel-sol transitions. The erosion and drug release kinetics from organogels under conventional (filling gelatin capsules) or multiparticulate (beads obtained by prilling) dosage forms were measured in simulated gastric and intestinal fluids. EFV release profiles were analyzed using model-dependent (curve-fitting) and independent approaches (Dissolution Efficiency DE). Korsmeyer-Peppas was the best fitting release kinetic model based on the goodness of fit, revealing a release mechanism from organogels loaded with EFV different from the simple drug diffusion release mechanism obtained from oily formulations. From organogels, EFV probably diffuses through an outer gel layer that erodes releasing oil droplets containing dissolved EFV into the aqueous medium.

摘要

本文提出了一种类固态体系,该体系由向日葵油构建而成,其结构中含有由12-羟基硬脂酸(12-HSA)组装形成的纤维状网络,12-HSA是一种油相胶凝剂分子。对所得的有机凝胶进行了研究,将其作为溶解于油中的亲脂性药物依法韦仑(EFV)的口服控释制剂。通过差示扫描量热法(DSC)研究了胶凝剂浓度对有机凝胶热性能的影响,结果表明药物掺入并未改变溶胶-凝胶-溶胶转变。在模拟胃液和肠液中测量了常规剂型(填充明胶胶囊)或多颗粒剂型(通过造粒获得的微丸)下有机凝胶的溶蚀和药物释放动力学。使用依赖模型(曲线拟合)和独立方法(溶出效率DE)分析了EFV的释放曲线。基于拟合优度,Korsmeyer-Peppas是最佳拟合释放动力学模型,揭示了载有EFV的有机凝胶的释放机制不同于从油性制剂获得的简单药物扩散释放机制。在有机凝胶中,EFV可能通过外层凝胶层扩散,该凝胶层溶蚀,将含有溶解的EFV的油滴释放到水性介质中。

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