Contact
    Start Publications Gastrointestinal diseases and their impact on drug solubility: ...
    ←  Publication Finder
    Attension

    Gastrointestinal diseases and their impact on drug solubility: Celiac disease

    Year: 2020

    Journal: Eur. J. Pharm. Sci., Volume 152, SEP 1

    Authors: Effinger, Angela; O'Driscoll, Caitriona M.; McAllister, Mark; Fotaki, Nikoletta

    Organizations: European Union's Horizon 2020 research and innovation programunder [674909]

    Keywords: Gastrointestinal diseases; Celiac disease; Biorelevant media; Physicochemical properties; Solubility

    The aim of this study was to develop an in vitro tool for predicting drug solubility and dissolution in intestinal fluids of patients with Celiac disease (CED). Biorelevant media for patients with CED were developed based on published information and a Design of Experiment (DoE) approach. The CED biorelevant media were char-acterised according to their surface tension, osmolality, dynamic viscosity and buffer capacity. By performing solubility studies of six drugs with different physicochemical properties in CED media, we aimed to identify drugs at high risk of altered luminal solubility in CED patients. Identified differences in CED patients compared to healthy subjects were related to a higher concentration of bile salts, lecithin and cholesterol and included as factors in the DoE resulting in 8 CED biorelevant media. Differences in media properties were observed for the surface tension between biorelevant media based on CED patients and healthy subjects. In terms of solubility, only a minimal effect of CED on the solubility of the hydrophilic neutral compound azathioprine was observed. For neutral moderately lipophilic compounds (budesonide, celecoxib), a higher surfactant concentration resulted in most cases in a higher drug solubility, while it was specific to each drug whether this was mainly driven by bile salts or lecithin. In comparison, drug solubilisation of ionisable compounds with moderate to high lipo-philicity was less impacted by CED differences. The developed biorelevant CED media serve as in vitro tool to identify the main media factors impacting on drug solubility.
    View publication