title: Importance of critical micellar concentration for the prediction of solubility enhancement in biorelevant media.
abstract: This study evaluated if the intrinsic surface properties of compounds are related to the solubility enhancement (SE) typically observed in biorelevant media like fasted state simulated intestinal fluids (FaSSIF). The solubility of 51 chemically diverse compounds was measured in FaSSIF and in phosphate buffer and the surface activity parameters were determined. This study showed that the compound critical micellar concentration parameter (CMC) correlates strongly with the solubility enhancement (SE) observed in FaSSIF compared to phosphate buffer. Thus, the intrinsic capacity of molecules to form micelles is also a determinant for each compound's affinity to the micelles of biorelevant surfactants. CMC correlated better with SE than lipophilicity (logD), especially over the logD range typically covered by drugs (2 < logD < 4). CMC can become useful to guide drug discovery scientists to better diagnose, improve, and predict solubility in biorelevant media, thereby enhancing oral bioavailability of drug candidates.
authors: ‡Roche Pharmaceutical Research and Early Development, Pharmaceutical Sciences, Roche Innovation Center Shanghai, F. Hoffmann-La Roche Ltd, 720 Cai Lun Road, Building 5 Pudong, Shanghai 201203, China.
authors: G
authors: G
authors: Ottaviani
authors: †Roche Pharmaceutical Research and Early Development, Pharmaceutical Sciences, Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd, Grenzacherstrasse 124, 4070 Basel, Switzerland.
authors: S
authors: S
authors: Wendelspiess
authors: †Roche Pharmaceutical Research and Early Development, Pharmaceutical Sciences, Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd, Grenzacherstrasse 124, 4070 Basel, Switzerland.
authors: R
authors: R
authors: Alvarez-Sánchez
mesh_terms: D001682:Biological Availability; D002021:Buffers; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D002851:Chromatography, High Pressure Liquid; D005215:Fasting; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007408:Intestinal Absorption; D007413:Intestinal Mucosa / Q000378:metabolism; D013058:Mass Spectrometry; D008823:Micelles; D010710:Phosphates / Q000737:chemistry; D012995:Solubility; D013056:Spectrophotometry, Ultraviolet; D013501:Surface-Active Agents / Q000737:chemistry; D013816:Thermodynamics
chemical_list: D002021:Buffers; D008823:Micelles; D010710:Phosphates; D013501:Surface-Active Agents
keywords: BCS; CMC; FaSSIF; FeSSIF; amphiphilicity; biorelevant media; critical micellar concentration; dissolution; lipophilicity; simulated intestinal fluids; solubility; surfactant