Keywords
Suspensions
Dissolution
Stability
How to Cite
Abstract
Amoxicillin is the drug of first choice for upper respiratory tract infections because it is better
absorbed orally compared to other beta-lactams antibiotics. The aim of this study was to conduct
stability studies of oral use extemporary suspensions amoxicillin according to RE 15
– ANVISA
from 29/07/05 and USP-35,6
as well as the perfomance in vitro through of the dissolution
properties, in the period indicated for use after reconstitution. Six samples have been obtained
randomly at Brazilian pharmaceutical market and another one at SUS distribution: being three
generic medicines of different manufacturers named G1, G2 and G3; three similar from different
manufacturers S1, S2 and S3 and 01 reference. The project included identification and amoxicillin
assay, pH, water content, and properties of dissolution to predict drug performance, in order to
complement previous studies. The results of the aspect of the powder and the suspensions, about
aspect, pH, water and assay were in compliance with USP specification 35 for the first and seventh
day after reconstitution. Although the amoxicillin assay has followed the specification on the
seventh day, it showed values up to 15% for degradation, that exceed the acceptance limits that is
0.1%, for maximum daily dose of ≤ 1 g, in disagreement to resolution RDC 53 of 2015. This study
verified possible failures in the performance of the suspension formulation of one of the seven
drugs tested (generic G3 with release of 50% amoxicillin on the seventh day after reconstitution in
the dissolution test), and may infer pharmacological problems of the formulation. The importance
of carrying out the stability study of the extemporaneous suspensions in the period indicated for the
use, to guarantee the effectiveness of the antimicrobial treatment and preventing the development
of bacterial resistance by the reduction of the dose to subtherapeutic levels due to problems in the
formulation, as well as the safety of use in relation to degradation products
References
Pronab KB, Winifred MC. Analytical Profiles of Drug Substances. New York: Klaus Florey;1978. p.19-22.
Martindale: The Complete Drug Reference. 34a ed. London: Sean C Sweetman, BPharm, FR PharmS; 2005. p.115-57.
WHO. International Stability Testing: guidelines for stability testing of pharmaceutical products containing well established drug substances in conventional dosage forms. WHO Technical Report Series. 863, 1996. WHO. Guidelines on Stability Testing: WHO Drug Information. v. 16. n. 1. Disponível em http://www.who.int/druginformation/ vol16num1 2002/vlo16-1.pdf
The United States Pharmacopeia USP-26 – The National Formulary NF 21. Rockville: United States Pharmacopeial Conventions; 2003. p. 2014-5. BEPA 2017;14(161):1-15 página 15 Verificação da estabilidade e do desempenho in vitro de suspensões extemporâneas de amoxicilina de medicamentos genéricos, similares e referência/Markman BEO et al.
Ministério da Saúde. Agência Nacional de Vigilância Sanitária. RE n.1 de 29/07/05 – Guia para realização de estudos de estabilidade. Brasília (DF); 2005, Disponível em: http://www.anvisa.gov.br/ medicamentos/legis/01_05_re_comentada. pdf. Acesso em: setembro 2015.
The United States Pharmacopeia USP-35 – The National Formulary NF 30. Rockville: United States Pharmacopeial Conventions; 2013. p. 2002.
Hsin H, Fe-Lin LW, Fu-Chang H, Hui-Yuan Y , Shu-Wen L, Li-Jiuan S. Effectiveness of Education Programs About Oral Antibiotic Suspensions in Pediatric Outpatient Services. Pediatr Neonatol. 2013; 54: 34-42.
The Pharmaceutical Codex: Principles and Pratices of Pharmaceuticals. 12 Ed., London: The Pharmaceutical Press; 1944. p.72-6.
Brown CK, Friedel HD, Barker AR, Buhse LF, Keitel S, Cecil TL, Kraemer J, Morris M, et al. FIP/AAPS Joint Workshop Report: Dissolution/In Vitro Release Testing of Novel/Special Dosage Forms. AAPS Pharm Sci Tech, 2011; 12(2):782-93.
Marques MRC, Vieira PF, Souza de Barros AC. Ensaios de dissolução e comparação de perfis de dissolução. In: A Regulação de Medicamentos no Brasil. Vieira PF, Rediguieri CF, Rediguieri CF. [Recurso eletrônico]. Organizadores, Vieira PF, Rediguieri CF, Rediguieri CF. Dados eletrônicos – Porto Alegre: Armed; 2013.
Marques MRC. Desenvolvimento e validação de métodos de dissolução para formas farmacêuticas sólidas orais. Rev. Analytica. 2002; 1: 48-51.
Markman BEO, Koschtschak MRW, Meihuey EW, Rosa PCP. Evaluation of the Quality and Stability of Amoxicillin Oral Suspension. J App Pharm Sci. 2014; 4(07): 38-40.
Ministério da Saúde. Agência Nacional de Vigilância Sanitária. Resolução RE n.899, de 29 de maio de 2003 ementa não oficial: Determina a publicação do “Guia para validação de métodos analíticos e bioanalíticos”. Brasília (DF); 2003.
Noman MA, Almeklafi SF, Kadi HO. Effect of different sources of water on the stability of amoxicillin trihydrate oral suspension in Yemen. Yemeni J for Med Sci. 2007; 67-76.
Ministério da Saúde Agência Nacional de Vigilância Sanitária, Resolução Da Diretoria Colegiada - RDC n.53, de 04 de dezembro de 2015. Estabelece parâmetros para a notificação, identificação e qualificação de produtos de degradação em medicamentos com substâncias ativas sintéticas e semissintéticas, classificados como novos, genéricos e similares, e dá outras providências. Brasília (DF);2015.
Ammar HO, Khalil RM. Discrepancy among dissolution rates of commercial tablets as a function dissolution method. Part 6: Rifampicin. Pharmazie. 1996; 51: 165-8.
Ammar HO et al. Discrepancy among dissolution rates of commercial tablets as a function dissolution method. Part 7: Aspirin. Pharmazie. 1997; 52: 145-9.
Vieira FP, Rediguieri CF, Rediguieri CF, (Organizador). A regulação de medicamentos no Brasil, 2013. In: Marques MRC; Vieira FP; Barros ACS. Ensaios de dissolução e comparação de perfis de dissolução. Porto Alegre: Artmed, 2013. Disponível em: Desenvolvimento de um teste de dissolução para comprimidos de nimesulida em meio que assegure condições sink
This work is licensed under a Creative Commons Attribution 4.0 International License.
Copyright (c) 2017 Blanca Elena Ortega Markman Ortega Markman, Fernanda Martini Graco, Elizabeth Wu Meihuey Wu Meihuey, Valeria Adriana Pereira Martins, Paulo César Pires Rosa