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

Ashmita Ramanah,Seeprarani Rath,Potiwa Purazi,Isadore Kanfer

doi:10.3390/scipharm88010006

Ashmita Ramanah, Seeprarani Rath + Show 2 more

Open Access

https://doi.org/10.3390/scipharm88010006

Copy DOI

Journal: Scientia Pharmaceutica	Publication Date: Feb 2, 2020
Citations: 3	License type: CC BY 4.0

Affiliation: Rhodes University, University of Toronto

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).

Highlights

Apart from the use of vasoconstrictor assay (VCA) for the bioequivalence assessment of topical corticosteroid products, comparative clinical trials are the only means whereby a generic company can demonstrate bioequivalence (BE) and/or bioavailability (BA) of most other topical dermatological dosage forms intended for local action [1]
The solubility of miconazole nitrate (MCZ) in the receptor medium was 3671 μg/mL (±60.24) which was more than 10 times higher than the highest measured concentration in the samples obtained during the method validation experiment (150 μg/mL)
A generic cream, Dermazole® cream (2%), showed “sameness” to the reference product: Daktarin® cream (2%), whereas another generic cream, Covarex® cream (2%), whose MCZ release rate did not fall within the acceptance criteria of 75–133.33% was considered not to be in vitro equivalent

Summary

Introduction

Apart from the use of vasoconstrictor assay (VCA) for the bioequivalence assessment of topical corticosteroid products, comparative clinical trials are the only means whereby a generic company can demonstrate bioequivalence (BE) and/or bioavailability (BA) of most other topical dermatological dosage forms intended for local action [1]. Expensive, and require a large number of participants and have resulted in a dearth of generic topical products reaching the market in both developed and developing countries [1,2]. The use of comparative clinical endpoints in patients is considered the least sensitive and reproducible approach among all other approaches to demonstrate BE [3]. Whereas clinical endpoint studies typically utilise a large sample size, they are often insensitive to formulation differences.

Objectives

Methods

Results

Conclusion