title: Influence of the physiological variability of fasted gastric pH and tablet retention time on the variability of in vitro dissolution and simulated plasma profiles.
abstract: The aim of the present study was to show that the physiological variability of fasted gastric pH and tablet gastric retention time contributes to the overall variability of simulated plasma profiles of diclofenac. Those two parameters were implemented into dissolution study and plasma profiles were simulated under assumptions that in vitro dissolution well represents that occurring in vivo, and that absorption profiles are identical to dissolution profiles, as diclofenac is a highly permeable drug. Dissolution experiments were performed using USP 2 apparatus and two consecutive dissolution media, namely, an acidic medium of various pH (ranging from 1-3), where tablets were kept for a certain time (10-200 min), and phosphate buffer (pH 6.8). It was shown that the acid pH value and acid retention time of tablets affect in vitro drug release, and consequently also influence the simulated plasma profiles. Lower acid pH resulted in lower plasma peaks at each studied acid retention time. Longer acid retention time caused lower plasma concentrations at lower acid pH values, whereas at pH 3 higher plasma concentrations were noted. Additionally, it was demonstrated that the variability of both parameters represents an important contribution to the overall variability of plasma profiles.
authors: Faculty of Pharmacy, University of Ljubljana, Aškerčeva cesta 7, 1000 Ljubljana, Slovenia. Electronic address: natasa.nageljkovacic@ffa.uni-lj.si.
authors: Nataša Nagelj
authors: NN
authors: Kovačič
authors: Faculty of Pharmacy, University of Ljubljana, Aškerčeva cesta 7, 1000 Ljubljana, Slovenia. Electronic address: mitja.pislar@ffa.uni-lj.si.
authors: Mitja
authors: M
authors: Pišlar
authors: Faculty of Pharmacy, University of Ljubljana, Aškerčeva cesta 7, 1000 Ljubljana, Slovenia. Electronic address: ilija.ilic@ffa.uni-lj.si.
authors: Ilija
authors: I
authors: Ilić
authors: Faculty of Pharmacy, University of Ljubljana, Aškerčeva cesta 7, 1000 Ljubljana, Slovenia. Electronic address: ales.mrhar@ffa.uni-lj.si.
authors: Aleš
authors: A
authors: Mrhar
authors: Faculty of Pharmacy, University of Ljubljana, Aškerčeva cesta 7, 1000 Ljubljana, Slovenia. Electronic address: marija.bogataj@ffa.uni-lj.si.
authors: Marija
authors: M
authors: Bogataj
mesh_terms: D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics; D003198:Computer Simulation; D004008:Diclofenac / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics; D065546:Drug Liberation; D005215:Fasting / Q000378:metabolism*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D065347:Hypromellose Derivatives / Q000737:chemistry; D007408:Intestinal Absorption; D008954:Models, Biological; D012995:Solubility; D013270:Stomach / Q000737:chemistry*; D013607:Tablets
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D013607:Tablets; D004008:Diclofenac; D065347:Hypromellose Derivatives
keywords: Diclofenac sodium; Gastric pH variability; In vitro dissolution; Pharmacokinetic variability; Plasma concentration profiles simulation; Tablets gastric retention time variability