Predicting the Pharmacokinetic behavior of Mangiferin using Gastro Plus and ADMET Predictor: Insights for Optimized Formulation Development

Gastro Plus, an in silico simulation software, predicts drug absorption behavior in humans and animals using an advanced compartmental absorption and transit model. This study explored the application of GastroPlus and ADMET Predictors to predict the pharmacokinetic behavior of mangiferin (MGF), a naturally occurring active pharmaceutical ingredient with diverse biological properties. The pharmaceutical applications of mangiferin are limited owing to its poor bioavailability. By utilizing GastroPlus along with the ADMET Predictor module, researchers have gained valuable insights into the behavior of MGF, assisting in the development of optimized formulations. A simulation using GastroPlus predicted the oral absorption and plasma concentration profile of MGF, showing poor bioavailability owing to first-pass metabolism and low absorption. Regional absorption indicated that the first part of the intestine may be the predominant site of MGF absorption. Calibration of the compartmental model with the in vivo and in vitro data validated the simulation results. Parameter sensitivity analysis identified solubility, permeability, and initial dose as the critical factors influencing the oral absorption of MGF. This study highlighted the significance of effective permeability (Peff) in enhancing MGF's bioavailability of MGF. Optimization of these factors may lead to the development of effective and bioavailable formulations of MGF. The combination of GastroPlus and ADMET Predictor may provide valuable insights into the pharmacokinetic behavior of MGF.