title: Evolution of a detailed physiological model to simulate the gastrointestinal transit and absorption process in humans, part II: extension to describe performance of solid dosage forms.
abstract: The physiological absorption model presented in part I of this work is now extended to account for dosage-form-dependent gastrointestinal (GI) transit as well as disintegration and dissolution processes of various immediate-release and modified-release dosage forms. Empirical functions of the Weibull type were fitted to experimental in vitro dissolution profiles of solid dosage forms for eight test compounds (aciclovir, caffeine, cimetidine, diclofenac, furosemide, paracetamol, phenobarbital, and theophylline). The Weibull functions were then implemented into the model to predict mean plasma concentration-time profiles of the various dosage forms. On the basis of these dissolution functions, pharmacokinetics (PK) of six model drugs was predicted well. In the case of diclofenac, deviations between predicted and observed plasma concentrations were attributable to the large variability in gastric emptying time of the enteric-coated tablets. Likewise, oral PK of furosemide was found to be predominantly governed by the gastric emptying patterns. It is concluded that the revised model for GI transit and absorption was successfully integrated with dissolution functions of the Weibull type, enabling prediction of in vivo PK profiles from in vitro dissolution data. It facilitates a comparative analysis of the parameters contributing to oral drug absorption and is thus a powerful tool for formulation design.
authors: Johann Wolfgang Goethe University, Institute of Pharmaceutical Technology, 60438 Frankfurt am Main, Germany. kirstin.thelen@bayer.com
authors: Kirstin
authors: K
authors: Thelen
authors: Katrin
authors: K
authors: Coboeken
authors: Stefan
authors: S
authors: Willmann
authors: Jennifer B
authors: JB
authors: Dressman
authors: Jörg
authors: J
authors: Lippert
mesh_terms: D003198:Computer Simulation; D004304:Dosage Forms; D041981:Gastrointestinal Tract / Q000378:metabolism; D005772:Gastrointestinal Transit; D006801:Humans; D007408:Intestinal Absorption; D008954:Models, Biological; D004364:Pharmaceutical Preparations / Q000008:administration & dosage; D010599:Pharmacokinetics; D012995:Solubility
chemical_list: D004304:Dosage Forms; D004364:Pharmaceutical Preparations