title: In vitro evaluation of the impact of gastrointestinal transfer on luminal performance of commercially available products of posaconazole and itraconazole using BioGIT.
abstract: Biorelevant Gastrointestinal Transfer system (BioGIT) has been shown to be useful in reproducing concentrations of drugs in the fasted upper small intestine after their administration in the stomach. In the present investigation, we evaluated the impact of gastrointestinal transfer on luminal performance of commercially available products of two highly lipophilic weak bases, posaconazole (Noxafil®suspension) and itraconazole (Sporanox®hard gelatin capsules and Sporanox®oral solution) by comparing % solid fraction, concentrations and supersaturation in the duodenal compartment of BioGIT with recently reported data in the upper small intestine of healthy adults. BioGIT was useful for estimating the % solid fraction in the upper small intestine, in cases where dissolution during gastric residence was incomplete, i.e. after administration of Noxafil®and Sporanox®capsules, and the precipitated fraction of itraconazole in the upper small intestine after administration of Sporanox®solution; median values in vitro were similar to the luminal values. Based on the values for the area under the concentration vs. time data estimated up to 45min post initiation of the experiment, concentrations in the duodenal compartment of BioGIT were similar to previously measured concentrations in the upper small intestine of healthy adults or they overestimated them by up to 2.5 times. In most cases, supersaturation of contents in the upper small intestine was overestimated, partly due to underestimation of luminal solubility.
authors.affiliation: Department of Pharmacy, National and Kapodistrian University of Athens, Zografou, Greece.
authors.forename: Alexandros
authors.initials: A
authors.lastname: Kourentas
authors.affiliation: Department of Pharmacy, National and Kapodistrian University of Athens, Zografou, Greece.
authors.forename: Maria
authors.initials: M
authors.lastname: Vertzoni
authors.affiliation: Department of Pharmacy, National and Kapodistrian University of Athens, Zografou, Greece.
authors.forename: Mira
authors.initials: M
authors.lastname: Symillides
authors.affiliation: Drug Delivery & Disposition, KU Leuven, Leuven, Belgium.
authors.forename: Bart
authors.initials: B
authors.lastname: Hens
authors.affiliation: Drug Delivery & Disposition, KU Leuven, Leuven, Belgium.
authors.forename: Joachim
authors.initials: J
authors.lastname: Brouwers
authors.affiliation: Drug Delivery & Disposition, KU Leuven, Leuven, Belgium.
authors.forename: Patrick
authors.initials: P
authors.lastname: Augustijns
authors.affiliation: Department of Pharmacy, National and Kapodistrian University of Athens, Zografou, Greece. Electronic address: reppas@pharm.uoa.gr.
authors.forename: Christos
authors.initials: C
authors.lastname: Reppas
mesh_terms: D002214:Capsules / Q000378:metabolism; D004386:Duodenum / Q000378:metabolism*; D005215:Fasting; D005753:Gastric Mucosa / Q000378:metabolism; D005772:Gastrointestinal Transit / Q000502:physiology; D006801:Humans; D007408:Intestinal Absorption / Q000502:physiology; D017964:Itraconazole / Q000378:metabolism*; D010634:Phenobarbital / Q000378:metabolism*; D012995:Solubility; D014230:Triazoles / Q000378:metabolism*
chemical_list: D002214:Capsules; D014230:Triazoles; D017964:Itraconazole; C101425:posaconazole; D010634:Phenobarbital
keywords: BioGIT; Dissolution; Itraconazole; Posaconazole; Precipitation; Supersaturation