Desenvolvimento de nova metodologia para avaliação da dissolução in vitro de comprimidos de Besilato de Amlodipina comercializados em Salvador/Bahia/Brasil, empregando planejamento experimental fatorial / Development of a new methodology for the evaluation of in vitro dissolution of Amlodipine Besylate tablets sold in Salvador /Bahia /Brazil, using factorial experimental design

Fernanda de Souza Dias, Gilmar Antônio de Carvalho Teles Júnior, João Luís Silva de Oliveira, Desirée Aguiar Bonfim, Jéssica Almeida Santos, Laura Beatriz Souza e Souza, Anderson Silva de Oliveira, Fábio de Souza Dias, Aníbal de Freitas Santos Júnior

Abstract


Besilato de amlodipino (AB) é um vasodilatador (bloqueador dos canais de cálcio) usado no tratamento da hipertensão arterial. Na Farmacopeia Brasileira (2019) não existem metodologias para avaliar a dissolução de comprimidos contendo este fármaco. O objetivo deste estudo foi, com base em um planejamento fatorial completo de dois níveis 23, desenvolver e validar um método de dissolução utilizando espectrofotometria na região ultravioleta para determinar AB, em comprimidos (5 mg) disponíveis como referência (R), similares (S) e genérico (G) comercializados em Salvador, Bahia, Brasil. O planejamento experimental foi utilizado para analisar três variáveis: rotação (rpm), concentração de HCl (mol L-1) e volume do meio de dissolução (mL). Os dados foram submetidos à análise de variância (ANOVA) e o gráfico de Pareto foi construído para análise de variáveis e suas interações. As variáveis estudadas não afetaram significativamente a liberação (%) de AB. Considerando a concentração e o pH fisiológico do líquido gástrico (entre 1,5 e 2,0), os princípios da química verde e impactos ambientais, as condições mínimas (50 rpm e 500 mL de HCl 0,001 mol L-1) foram selecionadas. Todos os produtos liberaram AB satisfatoriamente, com pelo menos 75% do fármaco dissolvido em 30 minutos. O método proposto apresentou boa linearidade (r = 0,9997); precisão (desvio padrão relativo <1,0%) e exatidão (recuperação média de 99,89%); limites de quantificação e detecção de 5,46 e 1,80 µg mL-1, respectivamente. Essa nova metodologia contribui com a Farmacopeia Brasileira e com o controle de qualidade das formas farmacêuticas orais sólidas da AB.

 

 


Keywords


perfis de dissolução, comprimidos de besilato de amlodipina, análise in vitro, planejamento experimental.

References


Şen, S.; Demir, M.; Yiğit, Z.; Üresin, A. Y. Efficacy and safety of s-amlodipine 2.5 and 5 mg/d in hypertensive patients who were treatment-naive or previously received antihypertensive monotherapy. J. Cardiovasc. Pharmacol. Ther. 2018, 23, 318–28. DOI: 10.1177/1074248418769054.

Sheraz, M. A.; Ahsan, S. F.; Khan, M. F.; Ahmed, S.; Ahmad, I. Formulations of amlodipine: a review. J. Pharm. (Cairo). 2016: 2016, 8961621. DOI: 10.1155/2016/8961621.

Rabhi, S.; Belkacemi, H.; Bououdina, M.; Kerrami, A.; Brahem, L. A.; Sakher, E. Effect of Ag doping of TiO2 nanoparticles on anatase-rutile phase transformation and excellent photodegradation of amlodipine besylate. Mater. Lett. 2019, 236, 640–43. DOI: 10.1016/j.matlet.2018.11.006.

Hussan, K. P. S.; Thayyil, M. S.; Rajan, V. K.; Muraleedharan, K. DFT studies on global parameters, antioxidant mechanism and molecular docking of amlodipine besylate. Comput. Biol. Chem. 2019, 80, 46–53. DOI: 10.1016/j.compbiolchem.2019.03.006.

Kapoor, H.; Aqil, M.; Imam, S. S.; Sultana, Y.; Ali, A. Formulation of amlodipine nano lipid carrier: formulation design, physicochemical and transdermal absorption investigation. J. Drug Deliv. Sci. Tec. 2019, 49, 209–18. DOI: 10.1016/j.jddst.2018.11.004.

Kaynak, M. S.; Bogacz, A.; Stelmasin´ski, M.; Şahin, S. Bioavailability file: amlodipine. FABAD J. Pharm. Sci. 2011, 36, 207–22.

Anumolu, P. D.; Neeli, S.; Anuganti, H.; Ranganatham, S. B. P.; Satya, S. C. V. Development of dissolution test method for a telmisartan/amlodipine besylate combination using synchronous derivative spectrofluorimetry. Braz. J. Pharm. Sci. 2014, 50, 329–36. DOI: 10.1590/S1984-82502014000200012.

Resolution of the Board of Directors – RDC No. 31. Ministry of Health, Brazilian Health Surveillance Agency (ANVISA): Brasília, August 11, 2010. Accessed Jan 04, 2020.http://portal.anvisa.gov.br/documents/33880/2568070/res0031_11_08_2010.pdf/5e157d15-d3d5-4bb9-98db-5667e4d9e0c8.

Resolution of the Board of Directors – RDC No. 16. Ministry of Health, Brazilian Health Surveillance Agency (ANVISA): Brasília, March 02, 2007. Accessed Jan 04, 2020.http://bvsms.saude.gov.br/bvs/saudelegis/anvisa/2007/rdc0016_02_03_2007.html.

Resolution of the Board of Directors – RDC No. 17. Ministry of Health, Brazilian Health Surveillance Agency (ANVISA): Brasília, March 02, 2007. Accessed Jan 04, 2020.http://bvsms.saude.gov.br/bvs/saudelegis/anvisa/2007/rdc0017_02_03_2007.html.

Brazilian Pharmacopeia, 6th ed.; Brasília: Brazilian Health Surveillance Agency; 2019.

Jambhekar, S. S.; Breen, P. J. Drug dissolution: significance of physicochemical properties and physiological conditions. Drug Discov. Today 2013, 18: 1173–84. DOI: 10.1016/j.drudis.2013.08.013.

Nickerson, B.; Kong, A.; Gerst, P.; Kao, S. Correlation of dissolution and disintegration results for an immediate-release tablet. J. Pharmaceut. Biomed. 2018, 150, 333–40. DOI: 10.1016/j.jpba.2017.12.017.

Todeschini, V.; Sangoi, M. S.; Goelzer, G. K.; Machado, J. C.; Paim, C. S.; Araujo, B.V.; Volpato, N. M. Dissolution method for delapril and manidipine combination tablets based on an absorption profile of manidipine. J. Pharm. Anal. 2016, 6, 49–55. DOI: 10.1016/j.jpha.2015.10.002.

Conceição, A. P.; Sá, R. R.; Silva, V. C.; Ferreira, M. S.; Cazedey, E. C. L.; Magalhães, H. I. F.; Santos Junior, A. F. A comparative study of propranolol release by in vitro dissolution profiles in pharmaceutical formulations. Dissolut. Technol. 2018, 25, 54–61. DOI: 10.14227/DT250418P54.

Kumar, L.; Reddy, M. S.; Managuli, R. S.; Pai K., G. Full factorial design for optimization, development and validation of HPLC method to determine valsartan in nanoparticles. Saudi Pharm J. 2015, 23, 549–55. DOI: 10.1016/j.jsps.2015.02.001.

Jain, A.; Jain, S. K. Formulation and optimization of temozolomide nanoparticles by 3 factor 2 level factorial design. Biomatter. 2013, 3, e25102. DOI: 10.4161/biom.25102.

Calado, V.; Montgomery, D. C. Planejamento de experimentos usando Statistica, 1th ed.; Rio de Janeiro: E-Papers Serviços Editoriais; 2003, pp 1–260.

The United States Pharmacopeia and National Formulary USP 41–NF 3640; The United States Pharmacopeial Convention, Inc.: Rockville, MD, 2018.

Khan, K. A. The concept of dissolution efficiency. J. Pharm. Pharmacol. 1975, 27, 48–49. DOI: 10.1111/j.2042-7158.1975.tb09378.x.

Resolution of the Board of Directors – RDC No. 166. Ministry of Health, Brazilian Health Surveillance Agency (ANVISA): Brasília, July 24, 2017. Accessed Jan 04, 2020. https://www20.anvisa.gov.br/coifa/pdf/rdc166.pdf.

International Conference on Harmonisation (ICH). International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use. ICH Q14: Analytical Procedure Development and Revision of Q2(R1)Analytical Validation; ICH Harmonised Tripartite Guideline: Geneva, Switzerland, 2018. Accessed Jan 4, 2020. https://database.ich.org/sites/default/files/Q2R2-Q14_EWG_Concept_Paper.pdf.

Attimarad, M.; Narayanswamy, V. K.; Aldhubaib, B. E.; SreeHarsha, N.; Nair, A. B. Development of UV spectrophotometry methods for concurrent quantification of amlodipine and celecoxib by manipulation of ratio spectra in pure and pharmaceutical formulation. PLoS One. 2019, 14, e0222526. DOI: 10.1371/journal.pone.0222526.

Zaid, A. N.; Al-Ramahi, R. J.; Ghoush, A. A.; Qaddumi, A.; Zaaror, Y. A. Weight and content uniformity of lorazepam half-tablets: a study of correlation of a low drug content product. Saudi Pharm. J. 2013, 21, 71–5. DOI: 10.1016/j.jsps.2011.12.009.

Rowe, R. C.; Sheskey, P. J.; Quinn, M. E. Handbook of pharmaceutical excipients, 6rd ed; London: Pharmaceutical Press, 2009, pp 1–917.

Banakar, U. V. Pharmaceutical Dissolution testing, New York: Marcel Dekker; 1992, pp 437.

Storpirtis, S.; Gonçalves, J. E.; Chiann, C.; Gai, M. N. Biopharmacotechnics, Rio de Janeiro: Guanabara Koogan; 2011, pp 35.

Martinez, R. M.; Silva, J. F.; Jorge, L. R.; Ishikawa, R. L.; Novelli, A. P.; Cezar, T. L. C.; Georgetti, S. R.; Baracat, M. M.; Casagrande, R. Validation of methodology for assay, pharmaceutical equivalence, and comparative dissolution profile for tablets containing amlodipine besylate. J. Appl. Pharm. Sci. 2019, 9, 93–100. DOI: 10.7324/JAPS.2019.91112.

Simionato, L. D.; Petrone, L.; Baldut, M.; Bonafede, S. L.; Segall. A. I. Comparison between the dissolution profiles of nine meloxicam tablet brands commercially available in Buenos Aires, Argentina. Saudi Pharm. J. 2018, 26, 578–84. DOI: 10.1016/j.jsps.2018.01.015.

Malesuik, M. D.; Cardoso, S. G.; Lanzanova, F. A.; Bajerski, L.; Dorigoni, E. Development of dissolution test and comparative study of tablets and compounded capsules containing amlodipine. Rev. Cienc. Farm. Basica Apl. 2006, 27, 37–49.

Kim, T. H.; Shin, S.; Jeong, S. W.; Lee, J. B.; Shin, B. S. Physiologically relevant in vitro-in vivo correlation (ivivc) approach for sildenafil with site-dependent dissolution. Pharmaceutics. 2019, 11, E251. DOI: 10.3390/pharmaceutics11060251.

Amidon, G. L.; Lennernas, H.; Shah, V. P.; Crison, J. R. A theoretical basis for a biopharmaceutic drug classification: the correlation of in vitro drug product dissolution and in vivo bioavailability. Pharm Res. 1995, 12, 413–20. DOI: 10.1023/a:1016212804288.

European Pharmacopoeia, 10th ed.; European Directorate for the Quality of Medicines & Healthcare, Council of Europe: Strasbourg, France, 2019.

Burges, R.; Moisey, D. Unique pharmacologic properties of amlodipine. Am. J. Cardiol. 1994, 73, 2A–9A. DOI: 10.1016/0002-9149(94)90268-2.

Shohin, I. E.; Ramenskaya, G. V.; Vasilenko, G. F.; Malashenko, E. A. In Vitro Dissolution Kinetics of Amlodipine Tablets Marketed in Russia Under Biowaiver Conditions. Dissolut. Technol. 2010, 17, 20–2. DOI: 10.14227/DT170310P20.

Food and Drug Administration (FDA) Draft Guidance for Industry, Waiver of In vivo bioavailability and bioequivalence studies for immediate-release solid oral dosage forms containing certain active moieties/active ingredients based on a biopharmaceutics classification system. February 1999, CDER/ FDA.

Feroz M.; Razvi, N.; Ghayas, S.; Anjum, F.; Ghazal, L.; Siddiqui, S. A. Assessment of pharmaceutical quality control and equivalence of various brands of amlodipine besylate (5 mg) tablets available in the Pakistani market under biowaiver conditions. Int. J. Pharm. Pharm. Sci. 2015, 6, 909–13.

Jung-Cook, H.; Mayet-Cruz, L.; Girard-Cuesy, M. E. Comparative in vitro dissolution and in vivo bioavailability of commercial amlodipine tablets. Trop. J. Pharm. Res. 2018, 17, 1685–91. DOI: 10.4314/tjpr.v17i9.1.

Olusola, A. M.; Olubukola, O. O.; Emeka, O. H.; Lilian, A. E. Equivalence of two generic brands of amlodipine besylate under biowaiver conditions. Int. J. Pharm. Pharm. Sci. 2012, 4, 265–68.




DOI: https://doi.org/10.34117/bjdv6n3-366

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