Clobetasol brazilian pilot study: the vasoconstrictor assay over time
DOI:
https://doi.org/10.1590/s2175-97902025e24597Keywords:
Vasoconstrictor Assay, Topical corticosteroids, Bioequivalence, Bioavailability, Topical drugs, ANVISAAbstract
The vasoconstrictor assay (VCA) has been internationally recognized as a reliable method to evaluate the bioequivalence of topical corticosteroids. The FDA has recommended its use since 1995 and ANVISA began to require this assay in 2022 (RDC no. 742/22). The objective of this study was to compare results from two VCA pilot studies, using two Konika Minolta® instruments and two different estimation methods. The Emax and ED50 parameters were obtained using a nonlinear mixed effect model and least squares fit using a Gauss-Newton algorithm. Regardless of the equipment or the fitting methods, similar Emax and ED50 were obtained. However, both parameters were different when comparing the assays performed from different batches of the same reference list drug (RLD) and procedures from the different guides. Added to this, the tests were carried out at different times and in different seasons. In the VCA pilot study, estimating the ED50 is essential to determine the D1 and D2 (shorter and longer dose duration reference standard calibrator) to be used in the pivotal bioequivalence study. The diversity of the Brazilian population and the lack of experience to perform the procedure represent major challenges for the implementation of this test.
Downloads
References
Aayushi BM, Nitin JN, Sharmila PP, Kiran VG, Manjyot G, Shweta A. Topical corticosteroids in dermatology. Indian J Dermatol Venereol Leprol. 2016;82:371.
ANVISA. Agência Nacional de Vigilância Sanitária. Farmacopeia Brasileira. Volume II. 6. Ed Brasília; 2019. Disponível em https://www.gov.br/ANVISA/pt-br/assuntos/farmacopeia/farmacopeia-brasileira/6aedicao-volume-2.
ANVISA. Agência Nacional de Vigilância Sanitária. Guia sobre requisitos de qualidade para produtos tópicos e transdérmicos - Guia nº 20/2019 – versão 2. Brasília, 2021. Disponível em: https://antigo.ANVISA.gov.br/documents/10181/5516542/Guia+t%C3%B3picos+e+transd%C3%A9rmicos+14+-+adequado+ao+novo+modelo+12.02.2021.pdf/38d9f16b-57ab-4ff5-a29c-4639c05e51da. Acesso de 23 de março de 2024.
Au WL. Investigations of the Bioavailability/Bioequivalence of Topical Corticosteroid Formulations containing Clobetasol Propionate using the Human Skin Blanching Assay, Tape Stripping and Microdialysis [Doctoral dissertation]. Grahamstown: Rhodes University, 2010.
Bodenlenz M, Tiffner KI, Raml R, Augustin T, Dragatin C, Birngruber T, et al. Open flow microperfusion as a dermal pharmacokinetic approach to evaluate topical bioequivalence. Clin Pharmacokinet. 2017;56:91-98.
Brasil. Departamento de Apoio à Gestão Participativa e ao Controle Social, Secretaria de Gestão Estratégica e Participativa, Ministério da Saúde. Política Nacional de Saúde Integral da População Negra: uma política para o SUS. 3ª Ed. Brasília: Editora do Ministério da Saúde; 2017.
Costin GE, Hearing VJ. Human skin pigmentation: melanocytes modulate skin color in response to stress. FASEB J. 2007;21(4):976-994.
Da Silva Júnior MAB, Da Fonseca Neto GC, Cabral JJSP. Análise estatística para detecção de tendências em séries temporais de temperatura e precipitação no Recife-PE. Revista de Geografia (Recife). 2020;37(1).
EMA. European Medicine Agency. Draft guideline on quality and equivalence of topical products. 2018.
Furukawa JY, Martinez RM, Morocho-Jácome AL, Castillo-Gomez TS, Pereda-Contreras VJ, Rosado C. Skin impacts from exposure to ultraviolet, visible, infrared, and artificial lights–a review. J Cosmet Laser The. 2021;23(1-2):1-7.
Gupta V, Sharma VK. Skin typing: Fitzpatrick grading and others. Clinics in dermatology. 2019;37(5):430-436.
Herkenne C, Alberti I, Naik A, Kalia YN, Mathy F, Préat V, et al. In vivo methods for the assessment of topical drug bioavailability. Pharm Res. 2008;25:87-103.
Humbert P, Guichard, A. The topical corticosteroid classification called into question: towards a new approach. Exp Dermatol. 2015;24(5):393-395.
Ilić T, Pantelić I, Savić S. The implications of regulatory framework for topical semisolid drug products: From critical quality and performance attributes towards establishing bioequivalence. Pharmaceutics. 2021;13(5):710.
Iliopoulos F, Caspers PJ, Puppels GJ, Lane ME. Franz cell diffusion testing and quantitative confocal raman spectroscopy: In vitro-in vivo correlation. Pharmaceutics. 2020;12(9):887.
Knorst MT. Desenvolvimento tecnológico de forma farmacêutica plástica contendo extrato concentrado de Achyrocline satureioides (Lam.) DC. [Masters Dissertation]. Porto Alegre: Universidade Federal do Rio Grande do Sul, 1991.
Leal LB, Araujo TP, Chagas SCC, Andrade ARB, Bedor DCG, Santana DP. Registro de medicamentos genéricos tópicos dermatológicos: cenário brasileiro e estudos para demonstração de bioequivalência. Vigil Sanit Debate, Rio de Janeiro. 2017;5(2):3-12.
Leal LB, Santana DP. Segunda fase da implantação de medicamentos genéricos no Brasil? Contract Pharma Brasil., Fev/2024 Disponível em: http://www.opera.art.br/clientes/Unite/revista_CPB_2024/news_02_fev/artigo.html. Acesso em 18/03/2024.
Mangas-Sanjuán V, Pleguezuelos V, Merino-Sanjuán M, Hernandéz MJ, Nácher A, García-Arieta A, et al. Assessment of the inter-batch variability of microstructure parameters in topical semisolids and impact on the demonstration of equivalence. Pharmaceutics. 2019;11(10):503.
Namjoshi, S, Dabbaghi, M, Roberts, MS, Grice JE, Mohammed, Y. Quality by design: Development of the quality target product profile (QTPP) for semisolid topical products. Pharmaceutics. 2020;12(3):287.
Nóbrega RS, Santos PFC, Moreira EBM. Morfologia urbana e ilhas de calor na cidade do Recife/PE: distribuição espacial e intensidade. Rev Geografia (Recife). 2016;33(4).
Núcleo de Desenvolvimento Farmacêutico (NUDFAC). Site institucional. Disponível em http://www.nudfacufpe.com.br/. Acessado em 23 de março de 2024.
Oliveira MMF. Radiação Ultravioleta/Índice Ultravioleta e câncer de pele no Brasil: Condições ambientais e vulnerabilidades sociais. Rev Bras Climatol. 2013;13(9):jul./dez.
Santos DJS, Palomares NB, Normando D, Quintão CCA. Raça versus etnia: diferenciar para melhor aplicar. Dent Press J Orthod. 2010;15:121-124.
Siska B, Snejdrova E, Machac I, Dolecek P, Martiska J. Contribution to the rheological testing of pharmaceutical semisolids. Pharm Dev Technol. 2019;24(1):80-88.
Shukla C, Bashaw ED, Stagni G, Benfeldt E. Applications of dermal microdialysis: a review. J Drug Deliv Sci Technol. 2014;24(3):259-269.
Simões A, Veiga F, Vitorino C. Progressing towards the sustainable development of cream formulations. Pharmaceutics. 2020;12(7):647.
Soares KCC, Santos GML, Gelfuso GM, Gratieri T. An update of the Brazilian regulatory bioequivalence recommendations for approval of generic topical dermatological drug products. AAPS J. 2015;17:1517-1518.
Suzuki HS, Hammerschmidt M, Kakizaki P, Mukai MM. Comparação do fototipo entre caucasianos e orientais. Surg Cosmet Dermatol. 2011;3(3):193-196.
United States of America, Federal Register - Code of Federal Regulations. Title 21 Part 320 - Bioavailability and Bioequivalence Requirements, Subpart B - Procedures for Determining the Bioavailability or Bioequivalence of Drug Products. Revised as 07 June 2023. Available from: https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?fr=320.24.
Food and Drug Administration (FDA). Department of Health and Human Services. Center of Drug Evaluation and Research (CDER). Guidance: Topic Dermatologic Corticosteroids: in Vivo Bioequivalence. Division of Bioequivalence, Office of Generic, Food and Drug Administration. 1995.
Food and Drug Administration (FDA). Department of Health and Human Services. Center of Drug Evaluation and Research (CDER). Guidance: Nonsterile Semisolid Dosage Forms: Scale-Up and Post Approval Changes: Chemistry, Manufacturing, and Controls; In Vitro Release Testing and In Vivo Bioequivalence Documentation. Division of Bioequivalence, Office of Generic, Food and Drug Administration. 1997. Available from: https://www.fda.gov/media/71141/download.
Food and Drug Administration (FDA). Department of Health and Human Services. Center of Drug Evaluation and Research (CDER). Guidance: Topic Dermatologic Corticosteroids: in Vivo Bioequivalence. Division of Bioequivalence, Office of Generic, Food and Drug Administration. 2022.
Food and Drug Administration (FDA). Department of Health and Human Services. Center of Drug Evaluation and Research (CDER). Guidance: Topic Dermatologic Corticosteroids: in Vivo Bioequivalence. Division of Bioequivalence, Office of Generic, Food and Drug Administration. 2023.
Wokovich AM, Prodduturi S, Doub WH, Hussain AS, Buhse LF. Transdermal drug delivery system (TDDS) adhesion as a critical safety, efficacy, and quality attribute. Eur J Pharm Biopharm. 2006;64(1):1-8.
Zvidzayi M, Rath S, Bon C, Abboo S, Kanfer I. A novel approach to assess the potency of topical corticosteroids. Pharmaceutics. 2021;13(9):1456.
Downloads
Published
Data Availability Statement
Declaração ausente.
Issue
Section
License
Copyright (c) 2025 Brazilian Journal of Pharmaceutical Sciences
This work is licensed under a Creative Commons Attribution 4.0 International License.
All content of the journal, except where identified, is licensed under a Creative Commons attribution-type BY.
The on-line journal has open and free access.
