Estudo de compatibilidade e avaliação da dissolução in vitro de formulações comerciais contendo fluconazol segundo os critérios da bioisenção
Autor(a) principal: | |
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Data de Publicação: | 2015 |
Tipo de documento: | Dissertação |
Idioma: | por |
Título da fonte: | Biblioteca Digital de Teses e Dissertações do UNICENTRO |
Texto Completo: | http://tede.unicentro.br:8080/jspui/handle/jspui/675 |
Resumo: | The biowaiver of bioequivalence studies on class I drugs of the biopharmaceutics classification system (BCS) is aimed mainly at reducing the costs and the exposure of health volunteers to a new pharmaceutical formulation. Fluconazole is an important antifungal agent but in the literature it is not clear whether it belongs to BCS class I or III. The aim of this study was to qualitatively determine the composition of commercially available fluconazole formulations in the form of capsules, to carry out compatibility studies drug/excipient, to develop and validate methodology by high performance liquid chromatography (HPLC) to quantify the drug and compare the in vitro dissolution profiles of reference, generic and similar formulations, verifing the compliance with the criteria established for biowaiver. One formulation did not contain sodium lauryl sulfate and contained mannitol, in contrast to the reference formulation, which could hinder the acceptance of the biowaiver. The interaction of fluconazole with microcrystalline cellulose and calcium hydrogen phosphate dihydrate was observed by Differential scanning calorimetry (DSC); however, no indication of incompatibility was found in the DSC analysis of the commercial pharmaceutical formulations. These interactions were also studied by Fourier transform infrared spectroscopy, where small changes in the bands were observed, and by X-ray Powder diffraction and scanning electron microscopy, that did not evidenced any modification in the solid state characteristics. The method developed and validated by HPLC to quantify the fluconazole showed linearity, specificity, precision, accuracy, satisfactory robustness and limits of quantification and detection, thus ensuring the reliability of the results. According to RDC 37/2011 to be a biowaiver candidate the formulation should be considered as rapid dissolution, i.e., not less than 85% of the total amount of drug contained in the formulation dissolves within 30 minutes. All tested formulations in simulated gastric fluid (pH1.2) met the specification. With acetate buffer (pH 4.5), all generic and one similar formulations complied the recommendations, and with simulated intestinal fluid (pH 6.8) only two generic and one similar showed a percentage of dissolution above 85%. Thus, it was shown that not all available commercial formulations met with the creteria established by RDC 37/2011. However, it should not be a concern for the patient, since they were subjected to in vivo analysis before approval by ANVISA. |
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Oliveira, Paulo Renato dehttp://lattes.cnpq.br/3167101952781896Bernardi, Larissa Sakishttp://lattes.cnpq.br/4786154799567952044.517.949-00http://lattes.cnpq.br/3239945150853599Teleginski, Lilian Klein2017-06-07T12:17:10Z2015-02-27Teleginski, Lilian Klein. Estudo de compatibilidade e avaliação da dissolução in vitro de formulações comerciais contendo fluconazol segundo os critérios da bioisenção. 2015. 74 f. Dissertação (Programa de Pós-Graduação em Ciências Farmacêuticas (Mestrado / Associação Ampla com UEPG) - Universidade Estadual do Centro-Oeste, Guarapuava - PR.http://tede.unicentro.br:8080/jspui/handle/jspui/675The biowaiver of bioequivalence studies on class I drugs of the biopharmaceutics classification system (BCS) is aimed mainly at reducing the costs and the exposure of health volunteers to a new pharmaceutical formulation. Fluconazole is an important antifungal agent but in the literature it is not clear whether it belongs to BCS class I or III. The aim of this study was to qualitatively determine the composition of commercially available fluconazole formulations in the form of capsules, to carry out compatibility studies drug/excipient, to develop and validate methodology by high performance liquid chromatography (HPLC) to quantify the drug and compare the in vitro dissolution profiles of reference, generic and similar formulations, verifing the compliance with the criteria established for biowaiver. One formulation did not contain sodium lauryl sulfate and contained mannitol, in contrast to the reference formulation, which could hinder the acceptance of the biowaiver. The interaction of fluconazole with microcrystalline cellulose and calcium hydrogen phosphate dihydrate was observed by Differential scanning calorimetry (DSC); however, no indication of incompatibility was found in the DSC analysis of the commercial pharmaceutical formulations. These interactions were also studied by Fourier transform infrared spectroscopy, where small changes in the bands were observed, and by X-ray Powder diffraction and scanning electron microscopy, that did not evidenced any modification in the solid state characteristics. The method developed and validated by HPLC to quantify the fluconazole showed linearity, specificity, precision, accuracy, satisfactory robustness and limits of quantification and detection, thus ensuring the reliability of the results. According to RDC 37/2011 to be a biowaiver candidate the formulation should be considered as rapid dissolution, i.e., not less than 85% of the total amount of drug contained in the formulation dissolves within 30 minutes. All tested formulations in simulated gastric fluid (pH1.2) met the specification. With acetate buffer (pH 4.5), all generic and one similar formulations complied the recommendations, and with simulated intestinal fluid (pH 6.8) only two generic and one similar showed a percentage of dissolution above 85%. Thus, it was shown that not all available commercial formulations met with the creteria established by RDC 37/2011. However, it should not be a concern for the patient, since they were subjected to in vivo analysis before approval by ANVISA.A bioisenção de estudos de bioequivalência para fármacos pertencentes à classe I do sistema de classificação biofarmacêutico (SCB) tem como principal objetivo a redução dos custos e da exposição de voluntários sadios a novas fórmulas farmacêuticas. O fluconazol é um agente antifúngico importante mas, na literatura, não está claro se ele pertence à classe I ou III do SCB. O objetivo do presente estudo foi determinar qualitativamente a composição de formulações de fluconazol disponíveis comercialmente sob a forma de cápsulas, realizar estudos de compatibilidade fármaco/excipiente, desenvolver e validar metodologia por cromatografia líquida de alta eficiência (CLAE) e comparar os perfis de dissolução in vitro de formulações referência, genéricas e similares para verificar o cumprimento dos critérios estabelecidos para a bioisenção. Na determinação qualitativa da composição das cápsulas, em relação à presença de excipientes críticos, uma fórmulação não continha lauril sulfato de sódio mas continha manitol, em contraste com a fórmula de referência, o que pode dificultar a aceitação da bioisenção. Na análise por Calorimetria Exploratória Diferencial foi observada interação entre o fluconazol e a celulose microcristalina e entre o fluconazol e o fosfato de cálcio dibásico diidratado. No entanto, nenhuma indicação de incompatibilidade foi encontrada na análise das fórmulas farmacêuticas comerciais. Essas interações também foram avaliadas por técnicas de espectroscopia no infravermelho com transformada de Fourier, onde pequenas alterações nas bandas foram observadas e por difração de raios X de pó e microscopia eletrônica de varredura, que não evidenciaram nenhuma modificação nas características do estado sólido. O método validado por CLAE mostrou-se linear, específico, preciso, exato, com robusez e limites de detecção e quantificação satisfatórios, garantindo assim a confiabilidade dos resultados. Segundo a RDC 37/2011, para ser candidato à bioisenção, um medicamento deve ser considerado de rápida dissolução, isto é, não menos de 85% da quantidade total do fármaco contido no medicamento deve se dissolver dentro de 30 minutos. Todas as formulações testadas em meio de fluido gástrico simulado (pH 1,2) cumpriram a especificação. Em tampão acetato (pH 4,5) apenas as formulações genéricas e uma similar cumpriram com o preconizado, e em meio de fluido intestinal simulado (pH 6,8), duas genéricas e uma similar apresentaram porcentagem de dissolução acima de 85%. Desta forma, demonstra-se que nem todas as formulações comerciais disponiveis cumpririam com o estabelecido pela RDC 37/2011, mas isto não deve ser uma preocupação para o paciente, uma vez que elas foram submetidas a análises in vivo para aprovação pela ANVISA.Submitted by Fabiano Jucá (fjuca@unicentro.br) on 2017-06-07T12:17:09Z No. of bitstreams: 1 Lilian Klein Teleginski.pdf: 2665986 bytes, checksum: 9baf945aeb70040b7754d003e5289ca0 (MD5)Made available in DSpace on 2017-06-07T12:17:10Z (GMT). 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dc.title.por.fl_str_mv |
Estudo de compatibilidade e avaliação da dissolução in vitro de formulações comerciais contendo fluconazol segundo os critérios da bioisenção |
title |
Estudo de compatibilidade e avaliação da dissolução in vitro de formulações comerciais contendo fluconazol segundo os critérios da bioisenção |
spellingShingle |
Estudo de compatibilidade e avaliação da dissolução in vitro de formulações comerciais contendo fluconazol segundo os critérios da bioisenção Teleginski, Lilian Klein bioisenção dissolução compatibilidade fluconazol biowaiver dissolution compatibility fluconazole CIENCIAS DA SAUDE::FARMACIA |
title_short |
Estudo de compatibilidade e avaliação da dissolução in vitro de formulações comerciais contendo fluconazol segundo os critérios da bioisenção |
title_full |
Estudo de compatibilidade e avaliação da dissolução in vitro de formulações comerciais contendo fluconazol segundo os critérios da bioisenção |
title_fullStr |
Estudo de compatibilidade e avaliação da dissolução in vitro de formulações comerciais contendo fluconazol segundo os critérios da bioisenção |
title_full_unstemmed |
Estudo de compatibilidade e avaliação da dissolução in vitro de formulações comerciais contendo fluconazol segundo os critérios da bioisenção |
title_sort |
Estudo de compatibilidade e avaliação da dissolução in vitro de formulações comerciais contendo fluconazol segundo os critérios da bioisenção |
author |
Teleginski, Lilian Klein |
author_facet |
Teleginski, Lilian Klein |
author_role |
author |
dc.contributor.advisor1.fl_str_mv |
Oliveira, Paulo Renato de |
dc.contributor.advisor1Lattes.fl_str_mv |
http://lattes.cnpq.br/3167101952781896 |
dc.contributor.advisor-co1.fl_str_mv |
Bernardi, Larissa Sakis |
dc.contributor.advisor-co1Lattes.fl_str_mv |
http://lattes.cnpq.br/4786154799567952 |
dc.contributor.authorID.fl_str_mv |
044.517.949-00 |
dc.contributor.authorLattes.fl_str_mv |
http://lattes.cnpq.br/3239945150853599 |
dc.contributor.author.fl_str_mv |
Teleginski, Lilian Klein |
contributor_str_mv |
Oliveira, Paulo Renato de Bernardi, Larissa Sakis |
dc.subject.por.fl_str_mv |
bioisenção dissolução compatibilidade fluconazol |
topic |
bioisenção dissolução compatibilidade fluconazol biowaiver dissolution compatibility fluconazole CIENCIAS DA SAUDE::FARMACIA |
dc.subject.eng.fl_str_mv |
biowaiver dissolution compatibility fluconazole |
dc.subject.cnpq.fl_str_mv |
CIENCIAS DA SAUDE::FARMACIA |
description |
The biowaiver of bioequivalence studies on class I drugs of the biopharmaceutics classification system (BCS) is aimed mainly at reducing the costs and the exposure of health volunteers to a new pharmaceutical formulation. Fluconazole is an important antifungal agent but in the literature it is not clear whether it belongs to BCS class I or III. The aim of this study was to qualitatively determine the composition of commercially available fluconazole formulations in the form of capsules, to carry out compatibility studies drug/excipient, to develop and validate methodology by high performance liquid chromatography (HPLC) to quantify the drug and compare the in vitro dissolution profiles of reference, generic and similar formulations, verifing the compliance with the criteria established for biowaiver. One formulation did not contain sodium lauryl sulfate and contained mannitol, in contrast to the reference formulation, which could hinder the acceptance of the biowaiver. The interaction of fluconazole with microcrystalline cellulose and calcium hydrogen phosphate dihydrate was observed by Differential scanning calorimetry (DSC); however, no indication of incompatibility was found in the DSC analysis of the commercial pharmaceutical formulations. These interactions were also studied by Fourier transform infrared spectroscopy, where small changes in the bands were observed, and by X-ray Powder diffraction and scanning electron microscopy, that did not evidenced any modification in the solid state characteristics. The method developed and validated by HPLC to quantify the fluconazole showed linearity, specificity, precision, accuracy, satisfactory robustness and limits of quantification and detection, thus ensuring the reliability of the results. According to RDC 37/2011 to be a biowaiver candidate the formulation should be considered as rapid dissolution, i.e., not less than 85% of the total amount of drug contained in the formulation dissolves within 30 minutes. All tested formulations in simulated gastric fluid (pH1.2) met the specification. With acetate buffer (pH 4.5), all generic and one similar formulations complied the recommendations, and with simulated intestinal fluid (pH 6.8) only two generic and one similar showed a percentage of dissolution above 85%. Thus, it was shown that not all available commercial formulations met with the creteria established by RDC 37/2011. However, it should not be a concern for the patient, since they were subjected to in vivo analysis before approval by ANVISA. |
publishDate |
2015 |
dc.date.issued.fl_str_mv |
2015-02-27 |
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2017-06-07T12:17:10Z |
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Teleginski, Lilian Klein. Estudo de compatibilidade e avaliação da dissolução in vitro de formulações comerciais contendo fluconazol segundo os critérios da bioisenção. 2015. 74 f. Dissertação (Programa de Pós-Graduação em Ciências Farmacêuticas (Mestrado / Associação Ampla com UEPG) - Universidade Estadual do Centro-Oeste, Guarapuava - PR. |
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http://tede.unicentro.br:8080/jspui/handle/jspui/675 |
identifier_str_mv |
Teleginski, Lilian Klein. Estudo de compatibilidade e avaliação da dissolução in vitro de formulações comerciais contendo fluconazol segundo os critérios da bioisenção. 2015. 74 f. Dissertação (Programa de Pós-Graduação em Ciências Farmacêuticas (Mestrado / Associação Ampla com UEPG) - Universidade Estadual do Centro-Oeste, Guarapuava - PR. |
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