In Vitro Release Testing Methodology and Variability with the Vertical Diffusion Cell (VDC)

Klein, Ryan R.; Heckart, Jenna L; Thakker, Kailas

doi:10.14227/dt250318p52

Cited by 13 publications

(10 citation statements)

References 19 publications

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“…The solubility of 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). The results confirmed that the solubility of MCZ in the receptor medium was sufficiently high to prevent saturation effects and to ensure sink conditions [19].…”

Section: Mcz Solubility In the Receptor Mediumsupporting

confidence: 70%

“…Aliquots of the supernatant were withdrawn, filtered, diluted and analysed to determine the concentration of the dissolved MCZ. Ideally, the solubility of the drug should be > 10 times the maximum expected concentration of the drug in the receptor medium throughout the IVRT run [19]. A duplicate set of control MCZ solutions without membranes was evaluated in parallel.…”

Section: Mcz Solubility In the Receptor Mediummentioning

confidence: 99%

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

et al. 2020

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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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Section: Mcz Solubility In the Receptor Mediumsupporting

confidence: 70%

Section: Mcz Solubility In the Receptor Mediummentioning

confidence: 99%

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

et al. 2020

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“…The receptor medium that had the most favorable outcome was ethanol:water (55/45 v/v), where the mean HCA solubility was 4447.4 µg/mL (CV = 6.38%). The latter concentration was more than 10 times the maximum expected concentration, as recommended (18).…”

Section: Membrane Screening and Receptor Fluid Selectionmentioning

confidence: 66%

In Vitro Release Testing (IVRT) of Topical Hydrocortisone Acetate Creams: A Novel Approach Using Positive and Negative Controls

Mudyahoto¹,

Rath²,

Ramanah³

et al. 2020

Dissolution Technol.

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The objective was to develop and validate an in vitro release testing (IVRT) method to assess the release of hydrocortisone acetate (HCA) from five topical formulations. A marketed generic cream containing 1% HCA was used as the reference product. Vertical diffusion cells (VDCs) were used to assess and compare the release rates of HCA from cream formulations containing 0.5%, 1%, and 1.5% HCA. The study describes a novel approach to test the discriminatory power by including both positive and negative controls to declare pharmaceutical equivalence or inequivalence. The validated method was found to be sensitive, linear, precise, reproducible, robust, and selective for the analysis of HCA from topical cream products. Equivalence or inequivalence was established based on SUPAC-SS acceptance criteria using a 90% CI with limits of 75-133.33%. The IVRT method was shown to have discriminatory ability to appropriately measure significant differences in drug release from various cream formulations. This approach also provides useful information for the future development of acceptable IVRT methods to assess topical dosage forms for local action containing different drugs.

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“…Although the observed solubilities of MTZ were >10 times the maximum expected concentration, as recommended [9], 0.9% NaCl solution was chosen as the receptor medium for subsequent studies, as it more appropriately reflects physiological conditions and is inexpensive and readily available. All the membranes except the Mixed Cellulose Ester membrane showed an acceptable recovery, indicating low MTZ binding.…”

Section: Discussionmentioning

confidence: 99%

“…Until recently, however, amongst the numerous publications involving the application of IVRT, comprehensive validation of IVRT systems and methods have been conspicuously absent from the literature. Although various efforts [8][9][10] have been made by several researchers to develop a standardized method to measure in vitro drug release from a product using diffusion cells, a comprehensive validation that would be generally applicable to all topical dermatological dosage forms has only recently been published [11]. This is essential to ensure that the developed IVRT method and the associated system has the necessary discriminatory capabilities to determine "sameness" between products and also, more importantly, differences, which may affect clinical performance.…”

Section: Introductionmentioning

confidence: 99%

A Validated IVRT Method to Assess Topical Creams Containing Metronidazole Using a Novel Approach

Rath

Kanfer

2020

Pharmaceutics

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An IVRT method was developed and validated to confirm its reproducibility, precision, sensitivity, selectivity, accuracy, robustness, and reliability. A novel approach was used to demonstrate the appropriateness of the IVRT method to accurately assess “sameness” between topical products and to confirm that the methodology applied also possesses the requisite discriminatory power to detect differences should such differences exist between products. In the first instance, the reference product (Metrocreme®) containing 0.75% metronidazole (MTZ) was tested against itself as a positive control, to accurately demonstrate “sameness”, where the results met the relevant acceptance criteria falling within the limits of 75–133.33% in accordance with the FDA’s SUPAC-SS guidance. In addition, two specially prepared creams containing 25% less and 26% more MTZ, i.e., 0.563% and 0.945%, served as negative controls and were compared against the reference product. Neither of these creams fell within the “sameness” acceptance criteria, thereby confirming the discriminatory ability of the IVRT method to detect differences between MTZ products. Furthermore, another cream containing 0.75% MTZ tested against the reference product was shown to be pharmaceutically equivalent to the reference product. These results confirm the appropriateness of the IVRT method as a valuable tool for use in the development of topical MTZ products intended for local action and indicate the potential for general use with other topical products.

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In Vitro Release Testing Methodology and Variability with the Vertical Diffusion Cell (VDC)

Cited by 13 publications

References 19 publications

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

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

In Vitro Release Testing (IVRT) of Topical Hydrocortisone Acetate Creams: A Novel Approach Using Positive and Negative Controls

A Validated IVRT Method to Assess Topical Creams Containing Metronidazole Using a Novel Approach

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