Assessment of “Sameness” and/or Differences between Marketed Creams Containing Miconazole Nitrate Using a Discriminatory in vitro Release Testing (IVRT) Method

Abstract

In vitro release testing (IVRT) provides an efficient method for the evaluation of drug release from semi-solid formulations. The aim of this research was to develop and validate a discriminatory IVRT system using vertical diffusion cells (VDCs) to assess generic topical products containing miconazole nitrate (MCZ). A comprehensive approach addressing all essential suitability criteria supporting the reliability of IVRT results was applied. These include mechanical validation of the VDCs, a performance verification test (PVT), validation of the analytical method (HPLC) used to quantify the drug release and validation of the IVRT method to confirm its precision, reproducibility, discriminatory ability, and robustness. Two marketed generic products were tested and assessed in accordance with the acceptance criteria for “sameness” in the FDA’s SUPAC-SS guidance which requires that the 90% confidence interval (CI) should fall within the limits of 75%–133.33%. One product was found to be in vitro equivalent to the reference product whereas the other was not. The results confirmed the suitability of the IVRT method to accurately measure the release of MCZ from topical cream products and, importantly, demonstrated the necessary discriminatory ability to assess “sameness”/differences of dermatological creams containing MCZ. Furthermore, the developed IVRT method was able to detect differences between formulations, which may be attributed to qualitative (Q1) and quantitative (Q2) properties and the microstructure and arrangement of matter (Q3).