title: The apparent solubilizing capacity of simulated intestinal fluids for poorly water-soluble drugs.
abstract: Drug solubility testing in biorelevant media has become an indispensable tool in pharmaceutical development. Despite this importance, there is still an incomplete understanding of how poorly soluble compounds interact with these media. The aim of this study was to apply the concept of the apparent solubilization capacity to fasted and fed state simulated intestinal fluid (FaSSIF and FeSSIF, respectively). A set of non-ionized poorly soluble compounds was studied in biorelevant media prepared from an instantly dissolving complex (SIF(™) Powder) at 37°C. The values of the solubilization capacity were different between FaSSIF and FeSSIF but correlated. Drug inclusion into the mixed micelles was highly specific for a given compound. The ratio of the FeSSIF to FaSSIF solubility was in particular considered and discussed in terms of the apparent solubilizing capacity. The apparent solubilization concept appears to be useful for the interpretation of biorelevant solubility tests. Further studies are needed to explore acidic and basic drugs.
authors.affiliation: Phares AG, Muttenz, Switzerland.
authors.forename: Hervé J
authors.initials: HJ
authors.lastname: Schwebel
authors.forename: Peter
authors.initials: P
authors.lastname: van Hoogevest
authors.forename: Mathew L S
authors.initials: ML
authors.lastname: Leigh
authors.forename: Martin
authors.initials: M
authors.lastname: Kuentz
mesh_terms: D001682:Biological Availability; D005215:Fasting; D005766:Gastrointestinal Contents / Q000737:chemistry*; D006801:Humans; D008823:Micelles; D008958:Models, Molecular; D009752:Nutritional Status; D010316:Particle Size; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D010599:Pharmacokinetics; D012995:Solubility; D014867:Water / Q000737:chemistry*
chemical_list: D008823:Micelles; D004364:Pharmaceutical Preparations; D014867:Water