title: In vitro--in silico--in vivo drug absorption model development based on mechanistic gastrointestinal simulation and artificial neural networks: nifedipine osmotic release tablets case study.
abstract: In vitro--in vivo correlations (IVIVC) are generally accepted as a valuable tool in modified release formulation development aimed at (i) quantifying the in vivo drug delivery profile and formulation related effects on absorption; (ii) establishing clinically relevant dissolution specifications and (iii) supporting the biowaiver claims. The aim of the present study was to develop relevant IVIVC models based on mechanistic gastrointestinal simulation (GIS) and artificial neural network (ANN) analysis and to evaluate their applicability and usefulness in biopharmaceutical drug characterisation. Nifedipine osmotic release tablets were selected as model drug product on the basis of their robustness, dissolution limited drug absorption and the availability of relevant literature data. Although the osmotic release tablets have been designed to be robust against the influence of physiological conditions in the gastrointestinal tract, notable differences in nifedipine dissolution kinetics were observed depending on the in vitro experimental conditions employed. The results obtained indicate that both GIS and ANN model developed were sensitive to input kinetics represented by the in vitro profiles obtained under various experimental conditions. Different in silico approaches may be successfully employed in the in vitro--in silico--in vivo model development. However, the results obtained may differ and relevant outcomes are sensitive to the methodology employed.
authors.affiliation: Department of Pharmaceutical Technology, University of Belgrade, Faculty of Pharmacy, Vojvode Stepe 450, 11221 Belgrade, Serbia.
authors.forename: Marija
authors.initials: M
authors.lastname: Ilić
authors.affiliation: Department of Pharmaceutical Technology, University of Belgrade, Faculty of Pharmacy, Vojvode Stepe 450, 11221 Belgrade, Serbia.
authors.forename: Jelena
authors.initials: J
authors.lastname: Ðuriš
authors.affiliation: Department of Pharmaceutical Technology, University of Belgrade, Faculty of Pharmacy, Vojvode Stepe 450, 11221 Belgrade, Serbia.
authors.forename: Ivan
authors.initials: I
authors.lastname: Kovačević
authors.affiliation: Department of Pharmaceutical Technology, University of Belgrade, Faculty of Pharmacy, Vojvode Stepe 450, 11221 Belgrade, Serbia.
authors.forename: Svetlana
authors.initials: S
authors.lastname: Ibrić
authors.affiliation: Department of Pharmaceutical Technology, University of Belgrade, Faculty of Pharmacy, Vojvode Stepe 450, 11221 Belgrade, Serbia. Electronic address: jelena.parojcic@pharmacy.bg.ac.rs.
authors.forename: Jelena
authors.initials: J
authors.lastname: Parojčić
mesh_terms: D003198:Computer Simulation; D041981:Gastrointestinal Tract / Q000378:metabolism; D006801:Humans; D007408:Intestinal Absorption; D008954:Models, Biological; D016571:Neural Networks, Computer; D009543:Nifedipine / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics*; D012995:Solubility; D013607:Tablets
chemical_list: D013607:Tablets; D009543:Nifedipine
keywords: Artificial neural network; Dissolution; Gastrointestinal simulation; In vitro – in vivo correlation; Nifedipine