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Reconstructed Human Epidermis: An Alternative Approach for In Vitro Bioequivalence Testing of Topical Products

The use of in vitro human skin permeation tests is of value when addressing the quality and equivalence of topical drug products in Europe and the US. Human skin is the membrane of choice for these studies. The use of human skin as a membrane is hindered by limited access, high variability of result...

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Autores principales: Agonia, Ana Sofia, Palmeira-de-Oliveira, Ana, Cardoso, Catarina, Augusto, Cátia, Pellevoisin, Christian, Videau, Christelle, Dinis-Oliveira, Ricardo Jorge, Palmeira-de-Oliveira, Rita
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9331624/
https://www.ncbi.nlm.nih.gov/pubmed/35893811
http://dx.doi.org/10.3390/pharmaceutics14081554
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author Agonia, Ana Sofia
Palmeira-de-Oliveira, Ana
Cardoso, Catarina
Augusto, Cátia
Pellevoisin, Christian
Videau, Christelle
Dinis-Oliveira, Ricardo Jorge
Palmeira-de-Oliveira, Rita
author_facet Agonia, Ana Sofia
Palmeira-de-Oliveira, Ana
Cardoso, Catarina
Augusto, Cátia
Pellevoisin, Christian
Videau, Christelle
Dinis-Oliveira, Ricardo Jorge
Palmeira-de-Oliveira, Rita
author_sort Agonia, Ana Sofia
collection PubMed
description The use of in vitro human skin permeation tests is of value when addressing the quality and equivalence of topical drug products in Europe and the US. Human skin is the membrane of choice for these studies. The use of human skin as a membrane is hindered by limited access, high variability of results, and limited applicability for drugs with low skin permeability. Reconstructed human epidermis (RhE) models are validated as skin surrogates for safety tests and have been explored for percutaneous absorption testing. Clotrimazole poorly permeates human skin and is widely available for topical treatments. In this study, clotrimazole creams were used to test the ability of RhE to be used as biological membrane for bioequivalence testing, based on the Draft Guideline on Quality and Equivalence of Topical Products (CHMP/QWP/708282/2018) using a discriminative and modified in vitro permeation test (IVPT). To fulfill the validation of a discriminatory method, Canesten(®) 10 mg/g cream was compared with a test product with the same drug strength, along with two “negative controls” dosed at a 50% and 200% drug strength. Products were compared in finite dose conditions, regarding maximal flux (J(max)) and the total amount of drug permeated (A(total)). The results showed the discriminatory power of the method among the three drug strengths with no interference of the placebo formulation. The study design and validation complied with the requirements established in the guideline for a valid IVPT. This new test system allowed for the equivalence comparison between test and comparator product. Higher permeability of the RhE compared to human skin could be observed. This arose as a strength of the model for this modified IVPT bioequivalence testing, since comparing permeation profiles among products is envisaged instead of drawing absolute conclusions on skin permeation extent. These results may support the acceptance of RhE as biological membranes for modified IVPT in bioequivalence testing of topical products.
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spelling pubmed-93316242022-07-29 Reconstructed Human Epidermis: An Alternative Approach for In Vitro Bioequivalence Testing of Topical Products Agonia, Ana Sofia Palmeira-de-Oliveira, Ana Cardoso, Catarina Augusto, Cátia Pellevoisin, Christian Videau, Christelle Dinis-Oliveira, Ricardo Jorge Palmeira-de-Oliveira, Rita Pharmaceutics Article The use of in vitro human skin permeation tests is of value when addressing the quality and equivalence of topical drug products in Europe and the US. Human skin is the membrane of choice for these studies. The use of human skin as a membrane is hindered by limited access, high variability of results, and limited applicability for drugs with low skin permeability. Reconstructed human epidermis (RhE) models are validated as skin surrogates for safety tests and have been explored for percutaneous absorption testing. Clotrimazole poorly permeates human skin and is widely available for topical treatments. In this study, clotrimazole creams were used to test the ability of RhE to be used as biological membrane for bioequivalence testing, based on the Draft Guideline on Quality and Equivalence of Topical Products (CHMP/QWP/708282/2018) using a discriminative and modified in vitro permeation test (IVPT). To fulfill the validation of a discriminatory method, Canesten(®) 10 mg/g cream was compared with a test product with the same drug strength, along with two “negative controls” dosed at a 50% and 200% drug strength. Products were compared in finite dose conditions, regarding maximal flux (J(max)) and the total amount of drug permeated (A(total)). The results showed the discriminatory power of the method among the three drug strengths with no interference of the placebo formulation. The study design and validation complied with the requirements established in the guideline for a valid IVPT. This new test system allowed for the equivalence comparison between test and comparator product. Higher permeability of the RhE compared to human skin could be observed. This arose as a strength of the model for this modified IVPT bioequivalence testing, since comparing permeation profiles among products is envisaged instead of drawing absolute conclusions on skin permeation extent. These results may support the acceptance of RhE as biological membranes for modified IVPT in bioequivalence testing of topical products. MDPI 2022-07-26 /pmc/articles/PMC9331624/ /pubmed/35893811 http://dx.doi.org/10.3390/pharmaceutics14081554 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/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 (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Agonia, Ana Sofia
Palmeira-de-Oliveira, Ana
Cardoso, Catarina
Augusto, Cátia
Pellevoisin, Christian
Videau, Christelle
Dinis-Oliveira, Ricardo Jorge
Palmeira-de-Oliveira, Rita
Reconstructed Human Epidermis: An Alternative Approach for In Vitro Bioequivalence Testing of Topical Products
title Reconstructed Human Epidermis: An Alternative Approach for In Vitro Bioequivalence Testing of Topical Products
title_full Reconstructed Human Epidermis: An Alternative Approach for In Vitro Bioequivalence Testing of Topical Products
title_fullStr Reconstructed Human Epidermis: An Alternative Approach for In Vitro Bioequivalence Testing of Topical Products
title_full_unstemmed Reconstructed Human Epidermis: An Alternative Approach for In Vitro Bioequivalence Testing of Topical Products
title_short Reconstructed Human Epidermis: An Alternative Approach for In Vitro Bioequivalence Testing of Topical Products
title_sort reconstructed human epidermis: an alternative approach for in vitro bioequivalence testing of topical products
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9331624/
https://www.ncbi.nlm.nih.gov/pubmed/35893811
http://dx.doi.org/10.3390/pharmaceutics14081554
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