Using Viscosity and In Vitro Release Test (IVRT) as Critical Quality Attributes (CQA) during a Generic Semi-solid Cream Product Development

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).

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In Vitro Release Test of Nano-drug Delivery Systems Based on Analytical and Technological Perspectives

Current Analytical Chemistry ◽

10.2174/1573411014666180912125931 ◽

2019 ◽

Vol 15 (4) ◽

pp. 373-409 ◽

Cited By ~ 2

Author(s):

Emirhan Nemutlu ◽

İpek Eroğlu ◽

Hakan Eroğlu ◽

Sedef Kır

Keyword(s):

Drug Delivery ◽

Analytical Method ◽

Drug Delivery Systems ◽

In Vitro Release ◽

Delivery Systems ◽

Method Selection ◽

Release Test ◽

Nano Drug Delivery ◽

Vitro Release

Background:Nanotech products are gaining more attention depending on their advantages for improving drug solubility, maintenance of drug targeting, and attenuation of drug toxicity. In vitro release test is the critical physical parameter to determine the pharmaceutical quality of the product, to monitor formulation design and batch-to-batch variation.Methods:Spectrophotometric and chromatographic methods are mostly used in quantification studies from in vitro release test of nano-drug delivery systems. These techniques have advantages and disadvantages with respect to each other considering dynamic range, selectivity, automation, compatibility with in vitro release media and cost per sample.Results:It is very important to determine the correct kinetic profile of active pharmaceutical substances. At this point, the analytical method used for in vitro release tests has become a very critical parameter to correctly assess the profiles. In this review, we provided an overview of analytical methods applied to the in vitro release assay of various nanopharmaceuticals.Conclusion:This review presents practical direction on analytical method selection for in vitro release test on nanopharmaceuticals. Moreover, precautions on analytical method selection, optimization and validation were discussed.

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