Gastrointestinal diseases and their impact on drug solubility: Celiac disease.

Gastrointestinal diseases and their impact on drug solubility: Celiac disease. Eur J Pharm Sci. 2020 Jul 06;:105460 Authors: Effinger A, O'Driscoll CM, McAllister M, Fotaki N Abstract 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 characterised 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 s...
Source: European Journal of Pharmaceutical Sciences - Category: Drugs & Pharmacology Authors: Tags: Eur J Pharm Sci Source Type: research