Session Speaker

Nanoparticle Dissolution and Absorption: Biopharmaceutics Physical Pharmacy, and Simulation
Michael B. Bolger
USA


The purpose of this seminar will be to discuss the theory and present examples of how drug nanoparticles (< 100 nm) behave differently than larger particles.
New chemical entities often have very low solubility, slow dissolution, and poor absorption. Formulation scientists sometimes use nanoparticle formulations to help overcome these limitations.

In some cases, in vivo studies using drug nanoparticles have shown some surprisingly large increases in AUC compared to larger particles. Until now, gastrointestinal simulation programs with standard dissolution and absorption equations are not able to accurately predict the in vivo results of drug nanoparticle formulations. Deviations from Nernst-Brunner dissolution and Ficks Law absorption rates are observed for some molecules.

GastroPlus™ was used to simulate the in vivo dissolution of nanoparticles based on the Kelvin equation. This equation describes changes in apparent solubility for very small particles and helps to explain the dissolution discrepancies. The Advanced Compartmental Absorption and Transit (ACAT) model was modified to allow nanoparticle formulations to achieve locally higher effective concentration gradients across the apical membrane of enterocytes.

This seminar will provide information regarding the latest theory and examples of experimental and computational simulation-based tools for understanding the mechanistic basis of nanoparticle dissolution and absorption.