title: A review of drug solubility in human intestinal fluids: implications for the prediction of oral absorption.
abstract: The purpose of this paper is to collate all recently published solubility data of orally administered drugs in human intestinal fluids (HIF) that were aspirated from the upper small intestine (duodenum and jejunum). The data set comprises in total 102 solubility values in fasted state HIF and 37 solubility values in fed state HIF, covering 59 different drugs. Despite differences in the protocol for HIF sampling and subsequent handling, this summary of HIF solubilities provides a critical reference data set to judge the value of simulated media for intestinal solubility estimation. In this regard, the review includes correlations between the reported solubilizing capacity of HIF and fasted or fed state simulated intestinal fluid (FaSSIF/FeSSIF). Correlating with HIF solubilities enables the optimal use of solubility measurements in simulated biorelevant media to obtain accurate estimates of intestinal solubility during drug development. Considering the fraction of poorly soluble new molecular entities in contemporary drug discovery, adequate prediction of intestinal solubility is critical for efficient lead optimization, early candidate profiling, and further development.
authors.affiliation: Drug Delivery and Disposition, KU Leuven, Leuven, Belgium. Electronic address: Patrick.Augustijns@pharm.kuleuven.be.
authors.forename: Patrick
authors.initials: P
authors.lastname: Augustijns
authors.affiliation: Drug Delivery and Disposition, KU Leuven, Leuven, Belgium.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Wuyts
authors.affiliation: Drug Delivery and Disposition, KU Leuven, Leuven, Belgium.
authors.forename: Bart
authors.initials: B
authors.lastname: Hens
authors.affiliation: Drug Delivery and Disposition, KU Leuven, Leuven, Belgium.
authors.forename: Pieter
authors.initials: P
authors.lastname: Annaert
authors.affiliation: Product Development, GlaxoSmithKline R&D, Harlow, UK.
authors.forename: James
authors.initials: J
authors.lastname: Butler
authors.affiliation: Drug Delivery and Disposition, KU Leuven, Leuven, Belgium.
authors.forename: Joachim
authors.initials: J
authors.lastname: Brouwers
mesh_terms: D000284:Administration, Oral; D001702:Biopharmaceutics / Q000379:methods*; D004304:Dosage Forms; D005215:Fasting / Q000378:metabolism; D018565:Food-Drug Interactions; D006801:Humans; D007408:Intestinal Absorption; D007419:Intestinal Secretions / Q000737:chemistry / Q000378:metabolism*; D007421:Intestine, Small / Q000378:metabolism*; D008954:Models, Biological; D010539:Permeability; D004364:Pharmaceutical Preparations / Q000008:administration & dosage* / Q000737:chemistry / Q000378:metabolism*; D010599:Pharmacokinetics; D019518:Postprandial Period; D012995:Solubility
chemical_list: D004304:Dosage Forms; D004364:Pharmaceutical Preparations
keywords: Duodenal solubility; Human intestinal fluid; Jejunal solubility; Oral absorption; Simulated intestinal fluid; Solubility