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Cutaneous Biodistribution: A High-Resolution Methodology to Assess Bioequivalence in Topical Skin Delivery

A draft guideline from the European Medicines Agency (EMA) highlights the need for methods to assess the quality/equivalence of topical drug formulations. The “cutaneous biodistribution method”, which provides insight into a drug’s spatial distribution in the epidermis/dermis, was used to compare cu...

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Autores principales: Quartier, Julie, Capony, Ninon, Lapteva, Maria, Kalia, Yogeshvar N.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6781275/
https://www.ncbi.nlm.nih.gov/pubmed/31540410
http://dx.doi.org/10.3390/pharmaceutics11090484
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author Quartier, Julie
Capony, Ninon
Lapteva, Maria
Kalia, Yogeshvar N.
author_facet Quartier, Julie
Capony, Ninon
Lapteva, Maria
Kalia, Yogeshvar N.
author_sort Quartier, Julie
collection PubMed
description A draft guideline from the European Medicines Agency (EMA) highlights the need for methods to assess the quality/equivalence of topical drug formulations. The “cutaneous biodistribution method”, which provides insight into a drug’s spatial distribution in the epidermis/dermis, was used to compare cutaneous bioavailability of econazole nitrate (ECZ) from a reference medicinal product (RMP) and two approved bioequivalent generic creams under finite dose conditions. Statistically significant differences between the ECZ biodistributions from the RMP/Generics were determined and used with acceptance criteria based on those from the EMA to evaluate bioequivalence. In porcine skin, ECZ deposition in total skin, epidermis, upper and lower dermis from Generic 1 was within the acceptance interval, contrary to Generic 2, which was marginally below it. For human skin, Generic 1 deposition was marginally above the acceptance interval and not bioequivalent. The results were consistent with those using the EMA’s acceptance intervals using the ratio of the mean ECZ depositions of Generic 1 and the RMP. Differences identified using this data-rich technique may not translate to observable differences in clinical efficacy; however, generics with non-statistically different biodistributions to the RMP should have a comparable clinical effect. The cutaneous biodistribution method could benchmark the development of topical generic products.
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spelling pubmed-67812752019-10-30 Cutaneous Biodistribution: A High-Resolution Methodology to Assess Bioequivalence in Topical Skin Delivery Quartier, Julie Capony, Ninon Lapteva, Maria Kalia, Yogeshvar N. Pharmaceutics Article A draft guideline from the European Medicines Agency (EMA) highlights the need for methods to assess the quality/equivalence of topical drug formulations. The “cutaneous biodistribution method”, which provides insight into a drug’s spatial distribution in the epidermis/dermis, was used to compare cutaneous bioavailability of econazole nitrate (ECZ) from a reference medicinal product (RMP) and two approved bioequivalent generic creams under finite dose conditions. Statistically significant differences between the ECZ biodistributions from the RMP/Generics were determined and used with acceptance criteria based on those from the EMA to evaluate bioequivalence. In porcine skin, ECZ deposition in total skin, epidermis, upper and lower dermis from Generic 1 was within the acceptance interval, contrary to Generic 2, which was marginally below it. For human skin, Generic 1 deposition was marginally above the acceptance interval and not bioequivalent. The results were consistent with those using the EMA’s acceptance intervals using the ratio of the mean ECZ depositions of Generic 1 and the RMP. Differences identified using this data-rich technique may not translate to observable differences in clinical efficacy; however, generics with non-statistically different biodistributions to the RMP should have a comparable clinical effect. The cutaneous biodistribution method could benchmark the development of topical generic products. MDPI 2019-09-18 /pmc/articles/PMC6781275/ /pubmed/31540410 http://dx.doi.org/10.3390/pharmaceutics11090484 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Quartier, Julie
Capony, Ninon
Lapteva, Maria
Kalia, Yogeshvar N.
Cutaneous Biodistribution: A High-Resolution Methodology to Assess Bioequivalence in Topical Skin Delivery
title Cutaneous Biodistribution: A High-Resolution Methodology to Assess Bioequivalence in Topical Skin Delivery
title_full Cutaneous Biodistribution: A High-Resolution Methodology to Assess Bioequivalence in Topical Skin Delivery
title_fullStr Cutaneous Biodistribution: A High-Resolution Methodology to Assess Bioequivalence in Topical Skin Delivery
title_full_unstemmed Cutaneous Biodistribution: A High-Resolution Methodology to Assess Bioequivalence in Topical Skin Delivery
title_short Cutaneous Biodistribution: A High-Resolution Methodology to Assess Bioequivalence in Topical Skin Delivery
title_sort cutaneous biodistribution: a high-resolution methodology to assess bioequivalence in topical skin delivery
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6781275/
https://www.ncbi.nlm.nih.gov/pubmed/31540410
http://dx.doi.org/10.3390/pharmaceutics11090484
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