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Complying with the Guideline for Quality and Equivalence for Topical Semisolid Products: The Case of Clotrimazole Cream

Semisolids constitute a significant proportion of topical pharmaceutical dosage forms available on the market, with creams being considered profitable systems for releasing active substances into the skin. This work aimed at the development of a generic Clotrimazole topical cream, based on the assum...

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Autores principales: Alves, Teresa, Arranca, Daniel, Martins, Ana, Ribeiro, Helena, Raposo, Sara, Marto, Joana
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8071103/
https://www.ncbi.nlm.nih.gov/pubmed/33920061
http://dx.doi.org/10.3390/pharmaceutics13040555
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author Alves, Teresa
Arranca, Daniel
Martins, Ana
Ribeiro, Helena
Raposo, Sara
Marto, Joana
author_facet Alves, Teresa
Arranca, Daniel
Martins, Ana
Ribeiro, Helena
Raposo, Sara
Marto, Joana
author_sort Alves, Teresa
collection PubMed
description Semisolids constitute a significant proportion of topical pharmaceutical dosage forms available on the market, with creams being considered profitable systems for releasing active substances into the skin. This work aimed at the development of a generic Clotrimazole topical cream, based on the assumptions that assist the development of such formulations. First, the critical parameters to obtain a final formulation as similar as possible to the reference product were defined. Then, the percentages of cetyl palmitate and octyldodecanol were identified as critical variables and chosen for optimization in further studies. A “quality by design” approach was then used to identify the effect of process variability on the structural and functional similarity (Q3) of the generic product qualitatively (Q1) and quantitatively (Q2). A two-factor central composite orthogonal design was applied and eleven different formulations were developed and subjected to physicochemical characterization and product performance studies. The results were used to estimate the influence of the two variables in the variation of the responses, and to determine the optimum point of the tested factors, using a design space approach. Finally, an optimized formulation was obtained and analysed in parallel with the reference. The obtained results agreed with the prediction of the chemometric analysis, validating the reliability of the developed multivariate models. The in vitro release and permeation results were similar for the reference and the generic formulations, supporting the importance of interplaying microstructure properties with product performance and stability. Lastly, based on quality targets and response constraints, optimal working conditions were successfully achieved.
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spelling pubmed-80711032021-04-26 Complying with the Guideline for Quality and Equivalence for Topical Semisolid Products: The Case of Clotrimazole Cream Alves, Teresa Arranca, Daniel Martins, Ana Ribeiro, Helena Raposo, Sara Marto, Joana Pharmaceutics Article Semisolids constitute a significant proportion of topical pharmaceutical dosage forms available on the market, with creams being considered profitable systems for releasing active substances into the skin. This work aimed at the development of a generic Clotrimazole topical cream, based on the assumptions that assist the development of such formulations. First, the critical parameters to obtain a final formulation as similar as possible to the reference product were defined. Then, the percentages of cetyl palmitate and octyldodecanol were identified as critical variables and chosen for optimization in further studies. A “quality by design” approach was then used to identify the effect of process variability on the structural and functional similarity (Q3) of the generic product qualitatively (Q1) and quantitatively (Q2). A two-factor central composite orthogonal design was applied and eleven different formulations were developed and subjected to physicochemical characterization and product performance studies. The results were used to estimate the influence of the two variables in the variation of the responses, and to determine the optimum point of the tested factors, using a design space approach. Finally, an optimized formulation was obtained and analysed in parallel with the reference. The obtained results agreed with the prediction of the chemometric analysis, validating the reliability of the developed multivariate models. The in vitro release and permeation results were similar for the reference and the generic formulations, supporting the importance of interplaying microstructure properties with product performance and stability. Lastly, based on quality targets and response constraints, optimal working conditions were successfully achieved. MDPI 2021-04-14 /pmc/articles/PMC8071103/ /pubmed/33920061 http://dx.doi.org/10.3390/pharmaceutics13040555 Text en © 2021 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
Alves, Teresa
Arranca, Daniel
Martins, Ana
Ribeiro, Helena
Raposo, Sara
Marto, Joana
Complying with the Guideline for Quality and Equivalence for Topical Semisolid Products: The Case of Clotrimazole Cream
title Complying with the Guideline for Quality and Equivalence for Topical Semisolid Products: The Case of Clotrimazole Cream
title_full Complying with the Guideline for Quality and Equivalence for Topical Semisolid Products: The Case of Clotrimazole Cream
title_fullStr Complying with the Guideline for Quality and Equivalence for Topical Semisolid Products: The Case of Clotrimazole Cream
title_full_unstemmed Complying with the Guideline for Quality and Equivalence for Topical Semisolid Products: The Case of Clotrimazole Cream
title_short Complying with the Guideline for Quality and Equivalence for Topical Semisolid Products: The Case of Clotrimazole Cream
title_sort complying with the guideline for quality and equivalence for topical semisolid products: the case of clotrimazole cream
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8071103/
https://www.ncbi.nlm.nih.gov/pubmed/33920061
http://dx.doi.org/10.3390/pharmaceutics13040555
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