title: Intestinal solubility and absorption of poorly water soluble compounds: predictions, challenges and solutions.
abstract: We have explored for which type of compounds biorelevant dissolution profiling in simulated intestinal fluids would accurately predict solubility in human intestinal fluid. In total, 474 solubility values in simulated and aspirated human intestinal fluid for 78 drugs were compiled and analyzed. Significant solubilization in the colloidal structures was obtained in fasted and fed state fluids for drug compounds with a logD(oct)>3. Highly lipophilic compounds with high melting points (Tm > 200 °C) could also be significantly solubilized, but typically such compounds had solubility values in the lower µg/ml range also in the presence of the colloidal structures. On the basis of our analysis, compounds with a logD(oct)>3 should be explored in biorelevant dissolution media to better predict in vivo performance after oral dosing.
authors: Department of Pharmacy, Uppsala University, Uppsala Biomedical Centre, PO Box 580, SE-751 23 Uppsala, Sweden.
authors: Jonas H
authors: JH
authors: Fagerberg
authors: Department of Pharmacy, Uppsala University, Uppsala Biomedical Centre, PO Box 580, SE-751 23 Uppsala, Sweden.
authors: Christel A S
authors: CA
authors: Bergström
mesh_terms: D001702:Biopharmaceutics / Q000145:classification; D001826:Body Fluids / Q000378:metabolism; D016503:Drug Delivery Systems; D006801:Humans; D007408:Intestinal Absorption; D007413:Intestinal Mucosa / Q000378:metabolism*; D004364:Pharmaceutical Preparations / Q000008:administration & dosage* / Q000737:chemistry*; D012995:Solubility
chemical_list: D004364:Pharmaceutical Preparations