Utility of physiologically based modeling and preclinical in vitro/in vivo data to mitigate positive food effect in a BCS class 2 compound.

ABSTRACT: Physiologically based pharmacokinetic (PBPK) modeling has become a useful tool to estimate the performance of orally administrated drugs. Here, we described multiple in silico/in vitro/in vivo tools to support formulation development toward mitigating the positive food effect of NVS123, a weak base with a pH-dependent and limited solubility. Administered orally with high-fat meal, NVS123 formulated as dry filled capsules displayed a positive food effects in humans. Three alternative formulations were developed and assessed in in vitro and in vivo preclinical and/or clinical studies. By integrating preclinical in vitro and in vivo data, the PBPK model successfully estimated the magnitude of food effects and the predicted values were within ± 30% of the observed results. A model-guided param

SUBMITTER: Xia B 

PROVIDER: S-EPMC3755159 | biostudies-literature | 2013 Sep

REPOSITORIES: biostudies-literature