In Silico Evaluation of the Biopharmaceutical and Pharmacokinetic Behavior of Metronidazole from Coated Colonic Release Matrix Tablets

Abstract

[EN]Background: Physiologically based biopharmaceutics modeling (PBBM) models can help to predict drug release and in vivo absorption behaviors. Colon drug delivery systems have gained interest over the past few years due to the advantages they provide in treating certain diseases in a local way. The objectives of this work were to simulate the biopharmaceutical and pharmacokinetic behavior of metronidazole hydrophilic matrices coated with different enteric polymers and to highlight the factors with a significant impact on the simulated pharmacokinetic parameters. Methods: Physicochemical properties of metronidazole were introduced into Simcyp® simulator platform, and the Advanced Dissolution Absorption Model (ADAM) was employed to simulate the in vivo intestinal absorption and colonic concentrations of metronidazole using a PBBM model. A Kruskal–Wallis test was carried out in order to determine which one of the factors studied has a statistically significant impact on the pharmacokinetic parameters (AUC, Cmax, and Tmax) simulated. Results: Enteric-coated matrix tablets are capable of avoiding metronidazole absorption in the small intestine and releasing it in the colonic region. The release and absorption rates of metronidazole depend largely on the percentage of weight gain of the coating and also on the coating agent. Coated tablets with a time-dependent coating show less variability. Conclusions: PBBM models can help predict the release from drug delivery systems and the pharmacokinetics in vivo of metronidazole from data obtained in vitro, although complementary in vivo studies should be needed.