Mechanistic Nucleation and Growth Can Predict Nonlinear Dose-Dependent Precipitation of Enabled Fomulations of Nimodipine in GastroPlus™
Simulation of precipitation can be important for accurate prediction of the absorption of many oral formulations. Amorphous solid dispersions, salt forms, cocrystals, solutions, and nanoparticles all can exhibit various levels of supersaturation leading to crystallization in vivo. In this work, we model the precipitation of nimodipine solid dispersions across three doses with a mechanistic nucleation and growth (MNG) model as well as with first-order precipitation kinetics. We compare results from the MNG model with first-order precipitation to show the benefits of the MNG model with respect to accurate simulation of the nonlinear magnitude and rate of precipitation due to dose escalation.
American Association of Pharmaceutical Scientists (AAPS), November 2-6, 2014, San Diego, CA
By Eva Huehn, Michael B. Bolger, James M. Mullin, Walter Woltosz