title: Biorelevant media simulating fed state intestinal fluids: colloid phase characterization and impact on solubilization capacity.
abstract: The purpose of the present study was to study the impact of free fatty acid and monoglyceride level and ratio on the nanostructural composition and solubilizing capacity of media simulating fed state intestinal fluids (SIFs). SIFs, without or with oleic acid/monoolein (OA/MO) in ratios of 2:1 or 6:1 were composed and characterized by surface tension, dynamic light scattering, and cryogenic transmission electron microscopy. Additionally solubilizing capacities towards three poorly water-soluble compounds: danazol, fenofibrate, and cinnarizine, were assessed. The surface tension of the media was not affected by the OA/MO ratio but only determined by the total surfactant concentration. The media with no lipolysis products only contained micelles, whereas media with lipolysis products also contained vesicles and other colloidal structures. The structures in the 6:1 media were more numerous and more well-defined regarding shape and size. The nanostructural composition of the media did influence the solubilizing capacity toward fenofibrate and cinnarizine, but not toward danazol. The relative composition of SIFs is important for the solubilizing capacity of some drug compounds. The findings in this study suggest that the affinity of the drug to the different colloidal structures is determining for the solubility of the compound in the media.
authors.affiliation: Department of Pharmaceutics and Analytical Chemistry, Faculty of Pharmaceutical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Karen
authors.initials: K
authors.lastname: Kleberg
authors.forename: Freja
authors.initials: F
authors.lastname: Jacobsen
authors.forename: Dimitris G
authors.initials: DG
authors.lastname: Fatouros
authors.forename: Anette
authors.initials: A
authors.lastname: Müllertz
mesh_terms: D000465:Algorithms; D001646:Bile / Q000737:chemistry; D001826:Body Fluids / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D002936:Cinnarizine / Q000737:chemistry; D003102:Colloids; D003613:Danazol / Q000737:chemistry; D004655:Emulsions; D005230:Fatty Acids, Nonesterified / Q000737:chemistry; D011345:Fenofibrate / Q000737:chemistry; D007413:Intestinal Mucosa / Q000378:metabolism*; D008027:Light; D008823:Micelles; D046529:Microscopy, Electron, Transmission; D050178:Monoglycerides / Q000737:chemistry; D010316:Particle Size; D012542:Scattering, Radiation; D012995:Solubility; D012996:Solutions; D013500:Surface Tension
chemical_list: D003102:Colloids; D004655:Emulsions; D005230:Fatty Acids, Nonesterified; D008823:Micelles; D050178:Monoglycerides; D012996:Solutions; D002936:Cinnarizine; D003613:Danazol; D011345:Fenofibrate