Prediction of in vivo performance of oral extended release (ER) formulations prior to clinical evolution: A case study for enteric coated polymeric beads formulation.

Abstract To reduce cost and time for product development, an ideal strategy for the development of oral extended release (ER) product is to identify the desired formulation with minimum needs for clinical evaluation. The aim of this work was to demonstrate the feasibility of adopting a “prediction-then-validation” strategy for the development of oral ER formulations. Instead of the traditional approach using multiple ER formulations for IVIVC development, an enteric-coated fast release formulation was successfully utilized for the development of a biopredictive tool to estimate the drug release from enteric coated polymeric ER formulations in the intestine. A TS1 (time scale factor between Tvitro and Tvivo equals to 1) system was designed and developed, based on which the in vivo pharmacokinetic (PK) performance of ER formulations in dog and in human were well predicted prior to in vivo evaluations. The model further passed a posteriori validation using the criteria for level A IVIVC and, as designed, provided a Tscale value of 1 for the IVIVC model.