Department of Pharmaceutical Sciences, College of Pharmacy, University of Michigan, Ann Arbor, MI 48109, USA; Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, Herestraat 49, 3000 Leuven, Belgium.
Department of Pharmaceutical Sciences, College of Pharmacy, University of Michigan, Ann Arbor, MI 48109, USA; Department Engineering Pharmacy Section, Miguel Hernandez University, San Juan de Alicante, 03550 Alicante, Spain.
Eur J Pharm Sci. 2018 Mar 30;115:258-269. doi: 10.1016/j.ejps.2018.01.039.
Supersaturating drug delivery systems (SDDS) have been put forward in the recent decades in order to circumvent the issue of low aqueous solubility. Prior to the start of clinical trials, these enabling formulations should be adequately explored in in vitro/in silico studies in order to understand their in vivo performance and to select the most appropriate and effective formulation in terms of oral bioavailability and therapeutic outcome. The purpose of this work was to evaluate the in vivo performance of four different oral formulations of posaconazole (categorized as a biopharmaceutics classification system (BCS) class 2b compound) based on the in vitro concentrations in the gastrointestinal simulator (GIS), coupled with an in silico pharmacokinetic model to predict their systemic profiles. Recently published intraluminal and systemic concentrations of posaconazole for these formulations served as a reference to validate the in vitro and in silico results. Additionally, the morphology of the formed precipitate of posaconazole was visualized and characterized by optical microscopy studies and thermal analysis. This multidisciplinary work demonstrates an in vitro-in silico-in vivo approach that provides a scientific basis for screening SDDS by a user-friendly formulation predictive dissolution (fPD) device in order to rank these formulations towards their in vivo performance.
在最近几十年中，为了解决低水溶性的问题，人们提出了药物超饱和输送系统（SDDS）。在开始临床试验之前，应该在体外/计算研究中充分探索这些使能制剂，以了解其体内性能，并根据口服生物利用度和治疗效果选择最合适和最有效的制剂。本工作的目的是基于胃肠道模拟器（GIS）中的体外浓度，评估泊沙康唑的四种不同口服制剂的体内性能（归类为生物药剂学分类系统（BCS） 2b 类化合物），并结合计算药代动力学模型来预测其系统特征。最近发表的这些制剂的泊沙康唑管腔内和系统内浓度被用作验证体外和计算结果的参考。此外，通过光学显微镜研究和热分析观察和表征了泊沙康唑形成的沉淀的形态。这项多学科工作展示了一种体外-计算-体内方法，为通过用户友好型制剂预测溶解（fPD）装置筛选 SDDS 提供了科学依据，以便根据其体内性能对这些制剂进行排序。
