Food and formulation characteristics are crucial factors affecting the gastrointestinal release and absorption kinetics of oral solid preparations. In the present study, the dynamic continuous release and bioaccessibility of metformin hydrochloride immediate-release (IR) and sustained-release (SR) tablets were investigated in the dynamic human stomach-intestine (DHSI-IV) system simulating fasted and fed states in healthy adults. Both tablet formulations (particularly IR tablet) exhibited a postponed release in the fed state compared to the fasted state. Correspondingly, the bioaccessible fraction of metformin from IR tablets in the presence of high-fat meal was significantly reduced to 76.2 % of the fasted state. However, the in vitro bioaccessibility was less impaired by food for SR tablets with a fed/fasted ratio of 95.5 %. A convolution-based approach was used to convert in vitro bioaccessibility results to plasma concentration data. The predicted plasma concentration curve showed good agreement with human data in terms of pharmacokinetic (PK) parameters. In the fasted state, the predicted Cmax, Tmax and AUC0-24h of IR tablets were 943.9 ± 25.7 ng/mL, 2.0 ± 0.4 h and 7090.7 ± 112.0 ng.h/mL, respectively, mirroring values observed in healthy subjects. Overall, the DHSI-IV system has demonstrated potential to assess and predict the impact of meal intake on the in vivo release and absorption behaviors of oral solid preparations.
Keywords: Dynamic dissolution; Food effect; In vitro gastrointestinal system; Metformin hydrochloride tablets; Oral dosage form; Plasma concentration prediction.
Copyright © 2024 Elsevier B.V. All rights reserved.