Development and Validation of IVIVR Models for Managing Formulation Changes in Immediate-Release Drug Products: A Case Study on Losartan Potassium 100 mg Tablets

The aim of the present study was to develop a tool to ensure that formulation changes do not compromise the quality or efficacy of a drug product.The study focused on the bioequivalent generic product LOSARTAN Potassium 100 mg immediate-release (IR) tablets.Prior to implementing changes to the marketed product, a validated mathematical modeling approach was employed to establish the relationship between in vivo and in vitro parameters.Specifically, the models were developed to link C max to % dissolution and AUC 0-t to % dissolution.The robustness of the developed IVIVR models was confirmed through successful validation and sensitivity testing.Sensitivity was assessed using five in-house IR formulations, with variations in the amount (0.5-8% w/w) of Sodium Starch Glycolate (SSG), a super-disintegrant, as well as Microcrystalline Cellulose and Maize Starch in the formulation of the marketed product.The results demonstrated that the IVIVR approach effectively detected formulation changes and provided reliable predictions of their impact.Consequently, this approach represents a highly relevant tool for controlling formulation modifications in marketed products for which bioequivalence studies have been conducted.