Evaluation and optimized selection of supersaturating drug delivery systems of posaconazole (BCS class 2b) in the gastrointestinal simulator (GIS): An in vitro-in silico-in vivo approach

Publication date: 30 March 2018
Source:European Journal of Pharmaceutical Sciences, Volume 115
Author(s): Bart Hens, Marival Bermejo, Yasuhiro Tsume, Isabel Gonzalez-Alvarez, Hao Ruan, Kazuki Matsui, Gregory E. Amidon, Katie L. Cavanagh, Gislaine Kuminek, Gail Benninghoff, Jianghong Fan, Naír Rodríguez-Hornedo, Gordon L. Amidon
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.

Graphical abstract

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