Drilling down the bioequivalence assessment of topical antifungal products: Microstructure and release

Miranda, Margarida; Cardoso, Catarina; Pais, Alberto; Brown, Marc; Vitorino, Carla

doi:10.1016/j.ejpb.2023.02.006

Cited by 4 publications

(2 citation statements)

References 19 publications

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“…The intra-batch and inter-time variabilities of the capsaicin emulsions were not excessively high, but given the changes in the mean values of the parameters experienced over time, the variability increases when batches of different shelf-lives are combined [ 10 ]. In bifonazole creams, no clear relationship between the changes in yield stress and the shelf-life were found and differences in their rheological parameters did not correlate with changes in the release of the active ingredient [ 8 ]. In contrast to these findings, our IVRT results showed a marked decrease in the fluxes obtained over time, mainly between the second and the third measurements.…”

Section: Resultsmentioning

confidence: 99%

“…Since the EMA published the above-mentioned draft, various publications have analyzed properties related to the microstructure and their relationship with the release profile in various semi-solid formulations, some identical and others that are clearly different, to evaluate the validity of the proposed criteria. Several studies [ 7 , 8 , 9 , 10 ] showed that the large variability observed in the rheological parameters does not allow the conclusion of equivalence of the structure of products that are known to be the same. These studies were conducted with a small number of batches and replicates per batch, and the products tested did not necessarily have the same age since manufacture at the time of evaluation.…”

Section: Introductionmentioning

confidence: 99%

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Impact of Time on Parameters for Assessing the Microstructure Equivalence of Topical Products: Diclofenac 1% Emulsion as a Case Study

Mañez-Asensi,

Hernández,

Mangas-Sanjuán

et al. 2024

Pharmaceutics

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The demonstration of bioequivalence proposed in the European Medicines Agency’s (EMA’s) draft guideline for topical products with the same qualitative and quantitative composition requires the confirmation of the internal structure equivalence. The impact of the shelf-life on the parameters proposed for internal structure comparison has not been studied. The objectives of this work were: (1) to quantify the effect of the time since manufacturing on the mean value and variability of the parameters proposed by the EMA to characterize the internal structure and performance of topical formulations of a complex topical formulation, and (2) to evaluate the impact of these changes on the assessment of the microstructure equivalence. A total of 5 batches of a topical emulgel containing 1% diclofenac diethylamine were evaluated 5, 14, and 23 months after manufacture. The zero-shear viscosity (η0), viscosity at 100 s−1 (η100), yield stress (σ0), elastic (G′) and viscous (G″) moduli, internal phase droplet size and in vitro release of the active ingredient were characterized. While no change in variability over time was detected, the mean value of all the parameters changed, especially the droplet size and in vitro release. Thus, combining data from batches of different manufacturing dates may compromise the determination of bioequivalence. The results confirm that to assess the microstructural similarity of complex formulations (such as emulgel), the 90% confidence interval limit for the mean difference in rheological and in vitro release parameters should be 20% and 25%, respectively.

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Section: Resultsmentioning

confidence: 99%