Revolutionizing Topical Drug Evaluation: A Discriminative and Validated In-Vitro Release Testing Paradigm for Mupirocin Cream 2%

The development of a robust and discriminative in-vitro release testing (IVRT) method for Mupirocin Cream 2% w/w was undertaken to support regulatory expectations for Q1/Q2 sameness and Q3 similarity in topical semisolid formulations. The method was designed using a vertical Franz diffusion cell system with a synthetic nylon membrane and optimized for sensitivity, specificity, and reproducibility. A comprehensive screening of receptor media identified USP buffer (pH 6.8): ethanol (70:30 v/v) as the most suitable medium, offering high solubility (675.88 µg/mL) and stability for Mupirocin. Membrane binding studies confirmed minimal drug retention, and pretreatment was deemed unnecessary. The method was validated using HPLC-UV detection at 222 nm, with a linearity range of 2.70–205.24 µg/mL (R² ≥ 0.999). Accuracy ranged from 95.56% to 101.48%, and precision (%RSD) was consistently below 3%. The method demonstrated excellent specificity, with no interference from placebo or blank matrices. Discriminatory power was established by evaluating release profiles of 50%, 100%, and 150% strength formulations. Confidence interval analysis confirmed equivalence for Test-02 and Test-03 with the reference product, while Test-01 was non-equivalent. Mass balance studies showed recovery between 91.1% and 99.4%, with drug depletion ranging from 11.5% to 13.3%. This validated IVRT method is suitable for routine quality control, formulation development, and regulatory submissions. It provides a sensitive and reliable tool for assessing the release characteristics of Mupirocin from semisolid matrices and supports the demonstration of bioequivalence in generic product development.