title: Fasted-state simulated intestinal fluid "FaSSIF-C", a cholesterol containing intestinal model medium for in vitro drug delivery development.
abstract: A set of biorelevant media "fasted-state simulated intestinal fluid with cholesterol (FaSSIF-C)" for the in vitro study of intestinal drug dissolution in the duodenum was developed. These contain cholesterol at the same levels as in human bile: the cholesterol content of FaSSIF-7C is equivalent to healthy female, FaSSIF-10C to healthy male persons, and FaSSIF-13C to several disease cases that lead to gallstones. The fluids were studied in three aspects: biocompatibility, intestinal nanostructure, and solubilizing power of hydrophobic drugs of the BCS class II. The biocompatibility study showed no toxic effects in a Caco-2 cell system. The drug-solubilizing capacity toward Fenofibrate, Danazol, Griseofulvin, and Carbamazepine was assessed as example. It varied with the cholesterol content widely from a fourfold improvement to a twofold reduction. The nanostructure study by dynamic light scattering and small-angle neutron scattering indicated vesicles as the main component of FaSSIF-C in equilibrium (>1 h), but at high cholesterol content, larger particles were observed as a minor contribution. The neutron experiments indicated the presence of complex micelle-vesicle mixtures, even after 1 h development of fed-state bile model to FaSSIF. The results indicate that cholesterol affects some drugs in solubilization and particle size in intestinal model fluids.
authors.affiliation: Johannes Gutenberg University, Pharmacy and Biochemistry Institute, Division Pharmaceutical Technology, Mainz, D-55099, Germany.
authors.forename: Pooneh
authors.initials: P
authors.lastname: Khoshakhlagh
authors.affiliation: Johannes Gutenberg University, Pharmacy and Biochemistry Institute, Division Pharmaceutical Technology, Mainz, D-55099, Germany.
authors.forename: Raphael
authors.initials: R
authors.lastname: Johnson
authors.affiliation: Johannes Gutenberg University, Pharmacy and Biochemistry Institute, Division Pharmaceutical Technology, Mainz, D-55099, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Langguth
authors.affiliation: Johannes Gutenberg University, Pharmacy and Biochemistry Institute, Division Pharmaceutical Technology, Mainz, D-55099, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Nawroth
authors.affiliation: Max Planck Institute for Polymer Research, Mainz, D-55128, Germany.|Johannes Gutenberg University, Molecular Biophysics Institute, Mainz, D-55128, Germany.
authors.forename: Lars
authors.initials: L
authors.lastname: Schmueser
authors.affiliation: Johannes Gutenberg University, Molecular Biophysics Institute, Mainz, D-55128, Germany.
authors.forename: Nadja
authors.initials: N
authors.lastname: Hellmann
authors.affiliation: Johannes Gutenberg University, Molecular Biophysics Institute, Mainz, D-55128, Germany.
authors.forename: Heinz
authors.initials: H
authors.lastname: Decker
authors.affiliation: Forschungszentrum Jülich GmbH, Jülich Centre for Neutron Science (JCNS) at Heinz Maier-Leibnitz Zentrum (MLZ), Garching, D-85747, Germany.
authors.forename: Noemi Kinga
authors.initials: NK
authors.lastname: Szekely
mesh_terms: D001826:Body Fluids / Q000378:metabolism*; D018938:Caco-2 Cells; D002220:Carbamazepine / Q000378:metabolism; D002784:Cholesterol / Q000378:metabolism*; D003613:Danazol / Q000378:metabolism; D016503:Drug Delivery Systems / Q000379:methods; D005215:Fasting / Q000378:metabolism*; D005260:Female; D011345:Fenofibrate / Q000378:metabolism; D006118:Griseofulvin / Q000378:metabolism; D006801:Humans; D007408:Intestinal Absorption / Q000502:physiology; D007413:Intestinal Mucosa / Q000378:metabolism*; D008297:Male; D008962:Models, Theoretical; D010316:Particle Size; D012995:Solubility
chemical_list: D006118:Griseofulvin; D002220:Carbamazepine; D002784:Cholesterol; D003613:Danazol; D011345:Fenofibrate
keywords: Caco-2 cells; DLS; FaSSIF; SANS; biorelevant media; drug solubility; in vitro models; light-scattering; lipids; micelle