Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
8514983 | Journal of Pharmaceutical Sciences | 2016 | 11 Pages |
Abstract
The purpose of this study was to assess the feasibility of a multicompartmental in vitro dissolution apparatus, gastrointestinal simulator (GIS), in assessing the drug dissolution of 2 commercially available oral dosage forms for itraconazole (ICZ). The GIS consists of 3 chambers, mimicking the upper gastrointestinal tract. In vitro dissolution of ICZ capsule or oral solution was evaluated in United States Pharmacopeia apparatus II and GIS. To investigate the suitability of fasted state simulated intestinal fluid (FaSSIF) to predict better in vivo, FaSSIF as well as phosphate buffer were used as dissolution media. Area under the dissolved drug amount-time curve (AUDC) was calculated for each dosage form in each apparatus, and the ratios of AUDCoral solution to AUDCcapsule were compared with human pharmacokinetic data. Based on this comparison, GIS with FaSSIF can adequately distinguish the pharmacokinetic profiles of 2 oral dosage forms for ICZ. Additionally, Caco-2 cell transepithelial transport study in combination with GIS revealed that improved drug dissolution by formulations resulted in enhanced permeation of ICZ through cell monolayer, suggesting the observed ICZ concentration in the GIS will directly reflect systemic exposure. These results indicate GIS would be a powerful tool to assess the formulations of ICZ as well as other Biopharmaceutics Classification System class II drug formulations.
Keywords
NaTCSIFTEERUSPSGFICZEMAFaSSIFHP-β-CDNaClPVDFHEPESPTFEFDAin vitro/in vivo correlations(4-(2-hydroxyethyl)-1-piperazineethanesulfonic acidsupersaturationAUCBSAbovine serum albuminEuropean Medicines agencyDissolutionUnited States PharmacopeiaItraconazolePrecipitationSodium taurocholateIntestinal absorptionfasted state simulated intestinal fluidGastrointestinalpolyvinylidene difluorideBCsFood and Drug AdministrationGISSodium chlorideCaco-2 cellsbiopharmaceutics classification systemcyclodextrinsSimulated intestinal fluidsimulated gastric fluidFormulationtransepithelial electrical resistancearea under the curvePermeabilitypolytetrafluoroethylene
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Pharmacology, Toxicology and Pharmaceutical Science
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Authors
Kazuki Matsui, Yasuhiro Tsume, Gregory E. Amidon, Gordon L. Amidon,