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Application of thermal analysis to the study of antituberculosis drugs–excipient compatibility

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Abstract

First-line drugs (rifampicin, RIF; isoniazid, INH; ethambutol, ETA; and pyrazinamide, PZA) recommended in conventional treatment of tuberculosis were analyzed in 1:1 w/w binary mixtures with microcrystalline cellulose MC 101 (CEL) and lactose supertab® (LAC) by differential scanning calorimetry (DSC), thermogravimetry (TG), differential thermal analysis (DTA), and Fourier transformed infrared analysis (FTIR) as part of development of fixed dose combination (FDC) tablets. Evidence of interaction between drug and pharmaceutical excipients was supposed when peaks disappearance or shifting were observed on DTA and DSC curves, as well as decreasing of decomposition temperature onset and TG profiles, comparing to pure species data submitted to the same conditions. LAC was showed to interact with RIF (absence of drug fusion and recrystallization events on DSC/DTA curves); INH (thermal events of the mixtures different from those observed for drug and excipient pure in DSC/DTA curves); PZA (decrease on drug fusion peak in DSC/DTA curves), and ETA (shift on drug onset fusion and absence of pure LAC events on DSC/DTA curves). In all cases, an important decrease on the temperature of drug decomposition was verified for the mixtures (TG analysis). However, FTIR analysis showed good correlation between theoretical and experimental drug-LAC spectra except for INH–LAC mixture, evidencing high incompatibility between these two species and suggesting that those interactions with PZA and RIF were thermally induced. No evidence of incompatibilities in CEL mixtures was observed to any of the four-studied drugs.

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Acknowledgments

The authors acknowledge to Universidade Federal do Rio Grande do Norte, UFRN and Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior, CAPES, for a fellowship Master Science.

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Authors and Affiliations

  1. Laboratório de Desenvolvimento de Medicamentos, Programa de Pós-Graduação em Ciências Farmacêuticas, Universidade Federal do Rio Grande Do Norte (UFRN), R. Brigadeiro Cordeiro de Farias, s/n, Petrópolis, Natal, RN, CEP 59010-180, Brazil

    Edilene Pereira Lavor

  2. Laboratório de Desenvolvimento de Medicamentos, Departamento de Farmácia, Universidade Federal do Rio Grande Do Norte (UFRN), R. Brigadeiro Cordeiro de Farias, s/n, Petrópolis, Natal, RN, CEP 59010-180, Brazil

    Fernanda Nervo Raffin & Túlio F. A. de Lima e Moura

  3. Programa de Pós-Graduação em Desenvolvimento e Inovação Tecnológica em Medicamentos, Universidade Federal do Rio Grande Do Norte (UFRN), Campus Universitário, s/n, Lagoa Nova, Natal, RN, CEP 59078-970, Brazil

    Marco Vinícius M. Navarro & Fátima D. Freire

  4. Laboratório de Quimica Farmaceutica, Departamento de Farmácia, Universidade Federal do Rio Grande Do Norte (UFRN), R. Brigadeiro Cordeiro de Farias, s/n, Petrópolis, Natal, RN, CEP 59010-180, Brazil

    Euzébio Guimarães Barbosa

  5. Laboratório de Controle de Qualidade de Medicamentos, Departamento de Farmácia, Universidade Federal do Rio Grande Do Norte (UFRN), R. Brigadeiro Cordeiro de Farias, s/n, Petrópolis, Natal, RN, CEP 59010-180, Brazil

    Cícero F. S. Aragão

Authors
  1. Edilene Pereira Lavor
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  2. Marco Vinícius M. Navarro
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  3. Fátima D. Freire
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  4. Cícero F. S. Aragão
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  5. Fernanda Nervo Raffin
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  6. Euzébio Guimarães Barbosa
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  7. Túlio F. A. de Lima e Moura
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Correspondence to Túlio F. A. de Lima e Moura.

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Lavor, E.P., Navarro, M.V.M., Freire, F.D. et al. Application of thermal analysis to the study of antituberculosis drugs–excipient compatibility. J Therm Anal Calorim 115, 2303–2309 (2014). https://doi.org/10.1007/s10973-013-3050-2

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  • DOI: https://doi.org/10.1007/s10973-013-3050-2

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