NIMESULIDE: DISSOLUTION PROFILE, VALIDATION OF ANALYTICAL METHODS FOR CAPSULES, AND ASSESSMENT OF PRODUCT QUALITY
Keywords:
Nimesulide, Dissolution profile, Validation, Capsules, Tablets, Compounding pharmacyAbstract
Objective: The main objective of this paper was to evaluate the quality of similar (S, n=3) and generic (G, n=3) tablets and compounding capsules (C, n=6) containing nimesulide (100 mg).
Methods: The parameters investigated (weight, nimesulide content, uniformity of dosage units, disintegration, friability and hardness (tablets) and dissolution profile) were evaluated against the Brazilian Pharmacopeia and a reference compound (for tablets). Nimesulide content, determined by a UV/visible spectrophotometric method, and dissolution test were validated for compounding capsules.
Results: All formulations had a mean weight coefficient of variation lower than 5%. Three compounding formulations contained less than 95 mg nimesulide, with C1 (88.5 mg) also showing a lack of dosage unit uniformity. Disintegration times were lower than 5 min for all samples and friability less than 0.5% for all tablet formulations. The hardness of the reference product (25.5N) was lower compared to the other tablet samples (30-80.3N). All tablet formulations reached 75% release after 5 min of the dissolution test, but none of the compounding formulations reached the minimum 75% release after 45 min, probably due to inadequate excipient composition and amount. On average, excipient accounted for 46.3% of the capsule weight (against 74% in tablets), and some of the products did not contain water-soluble substances to promote dissolution.
Conclusion: The results of this study indicate a lack of quality in compounding nimesulide products, which could jeopardize patients' health and treatment.
Â
Downloads
References
Sostres C, Gargallo CJ, Arroyo MT, Lanas A. Adverse effects of non-steroidal anti-inflammatory drugs (NSAIDs, aspirin and coxibs) on upper gastrointestinal tract. Best Pract Res Clin Gastroenterol 2010;24:121-32.
Carvalho WA. Anti-inflamatórios não esteroides, analgésicos, antipiréticos e drogas utilizadas no tratamentodagota. In: Farmacologia. 8th ed. Rio de Janeiro: Guanabara Koogan; 2010.
Korolkovas A, França FFAC. Dicionário Terapêutico Guanabara. 16th ed. Rio de Janeiro: Guanabara Koogan; 2009. p. 1.
Rainsford KD. Nimesulide–a multifactorial approach to inflammation and pain: scientific and clinical consensus. Curr Med Res Opin 2006;22:1161-70.
Reddy BBK, Karunakar A. Biopharmaceutics classification system: a regulatory approach. Dissolution Technol 2011;18:31-7.
Silva RL, Volpato NM. Meios para dissolução de comprimidos de nimesulida: Ação dos tensoativos. Braz J Pharm Sci 2002;38:163-72.
Ruela AL, Araújo MB, Pereira GR. Desenvolvimento de um teste de dissolução para comprimidos de nimesulida em meio que assegure condições sink. Lat Am J Pharm 2009;28:661-7.
Bai G, Wang Y, Armenante PM. Velocity profiles and shear strain rate variability in the USP dissolution testing apparatus 2 at different impeller agitation speeds. Int J Pharm 2011;403:1-14.
Ferraz CC, Silva MLO, Vila MMDC, Oliveira RVM, Farina SS. Evaluation of quality control in pharmacies with handling in the city of Sorocaba, SP. Res Exp Undergraduates 2008;34:135-48.
Ferreira AO, Brandão MAF. Controle de qualidade na farmácia magistral-especificação de matérias-primas, leitura crÃtica dos certificados de análise; 2008. Available from: http://www.latamjpharm.org/trabajos/27/4/LAJOP_27_4_1_12 5N7R7V9ZZK.pdf [Last accessed on 09 Dec 2015]
Gudeman J, Jozwiakowski M, Chollet J, Randell M. Potential risks of pharmacy compounding. Drugs RD 2013;13:1-8.
United States Food and Drug Administration (USFDA). The special risks of pharmacy compounding; 2012. Available from: http://www.fda.gov/ForConsumers/ConsumerUpdates/ucC107836.htm. [Last accessed on 09 Dec 2015].
National Health Surveillance Agency (ANVISA). Resolução da Diretoria Colegiada–RDC No. 67, de 8 de Outubro de. Dispõe sobre Boas Práticas de Manipulação de preparações magistrais e officials para uso humano em farmácias; 2007.
International Conference on Harmonization. Validation of analytical procedures: text and methodology Q2(R1). Geneva: IFPMA; 2005. Available from: http://www.ich.org/fileadmin/ Public_Web_Site/ICH_Products/Guidelines/Quality/Q2_R1/Step4/Q2_R1__Guideline. pdf. [Last accessed on 09 Dec 2015].
Brazilian Pharmacopeia. 5th ed. BrasÃlia, National Health Surveillance Agency (ANVISA); 2010.
British Pharmacopeia, London, The Stationery Office; Medicines and Healthcare products Regulatory Agency; 2012.
United States Pharmacopeia. 35th ed. United States Pharmacopoeial Convention: Rockville; 2011.
Menegola J, Steppe M, Schapoval EES. Dissolution test for citalopram in tablets and comparison of in vitro dissolution profiles. Eur J Pharm Biopharm 2007;67:524-30.
Food and Drug Administration: Center for Drug Evaluation and Research. Extended Release Oral Dosage Forms: Development, Evaluation, and Application of In vitro/In vivo Correlations. Guidance for Industry, U. S. Department of Health and Human Services. Government Printing Office: Washington; 1997.
Dutra VC. Manipulação de cápsulas. Serviço Brasileiro de Respostas Técnicas. Rede de Tecnologia e Inovação do Rio de Janeiro; 2012.
Lu Y, Kim S, Park K. In vitro–in vivo correlation: Perspectives on model development. Int J Pharm 2011;418:142-8.
Freitag G. Guidelines on dissolution profile comparison. Drug Inf J 2001;35:865–74.
Souza J, Freitas ZMF, Storpirtis S. In vitro models for the determination of drug absorption and a prediction of dissolution/absorption relationships. Braz J Pharm Sci 2007;4:515-27.
Anderson NH, Bauer M, Boussac N, Khan-Malek R, Munden P, Sardaro M. An evaluation of fit factors and dissolution efficiency for the comparison of in vitro dissolution profiles. J Pharm Biomed 1998;17:811-22.
Costa P, Lobo JMS. Modeling and comparison of dissolution profiles. Eur J Pharm Sci 2001;13:123-33.
Allen VL, Popovich NG, Ansel HC. Ansel’s pharmaceutical dosage forms and drug delivery systems. 9th ed. Philadelphia: Lippincott Williams and Wilkins; 2011.
Ashford M. Biodisponibilidade–Fatores FÃsico-quÃmicos e Relacionados à Forma Farmacêutica. In: Delineamento de Formas Farmacêuticas, Aulton ME. 2nd ed. Porto Alegre (Brazil): Artmed; 2005.
Kubbingaa M, Moghani L, Langguth P. Novel insights into excipient effects on the biopharmaceutics of APIs from different BCS classes: Lactose in solid oral dosage forms. Eur J Pharm Sci 2014;61:27-31.