Developing a predictive in vitro dissolution model based on gastrointestinal fluid characterisation in rats.

Developing a predictive in vitro dissolution model based on gastrointestinal fluid characterisation in rats. Eur J Pharm Biopharm. 2019 Jul 06;: Authors: Fjelrad Christfort J, Strindberg S, Plum J, Hall-Andersen J, Janfelt C, Hagner Nielsen L, Müllertz A Abstract The influence of physiological factors on the solubility of drug compounds has been thoroughly investigated in humans. However, as these factors vary between species and since many in vivo studies are carried out in rats or mice, it has been difficult to establish sufficient in vitro in vivo relations. The aim of this study was to develop a physiologically relevant in vitro dissolution model simulating the gastrointestinal (GI) fluids of fasted rats and compare it to previously published in vitro and in vivo data. To develop the in vitro model, the pH was measured in situ in six segments of the GI tract of anesthetised rats, then the fluids from the stomach, the proximal and the distal small intestine were collected and characterized with regard to osmolality, and bile acid and phospholipid concentration. The pH and osmolality were found to increase throughout the GI tract. The bile acids and phospholipids were present in high concentrations in the proximal small intestine, and the bile acid concentration doubled in the distal part, where the phospholipid concentration decreased. Matrix-assisted laser desorption ionisation mass spectrometry imaging was applied on a cross se...
Source: European Journal of Pharmaceutics and Biopharmaceutics - Category: Drugs & Pharmacology Authors: Tags: Eur J Pharm Biopharm Source Type: research