Pharmacokinetic bioequivalence studies of a new Etoricoxib tablet formulation developed using proprietary MiST technology — risk assessment and mitigation using GastroPlus software

Introduction: In this work, we present model guided development of a new Etoricoxib tablet formulation using a proprietary technology. Application of absorption modelling using GastroPlus to guide the product development process is presented. An integrated approach of using in vitro, modelling and in vivo pharmacokinetics (PK) data to demonstrate bioequivalence between newly developed formulation and the commercial formulation is presented. Methods: The MiSTTM technology is a combination of wetting-solubilizing agents with suspension-spray granulation technique. A physiologically-based biopharmaceutics model (PBBM) coupled with population PK and virtual bioequivalence was employed to guide the product development process. Commercially available GastroPlus 9.8 software was used for this purpose. Results: Based on the simulation outcome, it was concluded that the new cost-effective formulation manufactured using MiSTTM technology could be bioequivalent against the marketed formulation. This was further confirmed from the in vivo PK studies in normal healthy volunteers. Conclusion: The simulated data were in line with the observed PK data obtained from the in-house bioequivalence study. This work demonstrates application of predictive modelling and simulation tools to accelerate new product development