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Characterization and thermal stability study of efavirenz and solid dispersion with PVPVA 64 by means of thermal analysis and pyrolysis coupled with GC/MS

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Abstract

The acquired immunodeficiency syndrome remains a major problem in worldwide public health and its antiretroviral treatment therapy combines at least three high activity classes of drugs. Access to antiretroviral treatment for HIV-infected patients is a global public health priority and efavirenz (EFZ) is one of the first drug choices. However, EFZ is classified as a class II drug, according to the biopharmaceutics classification system due to low solubility and high permeability, which leads it to fail in absorption and hence bioavailability. One of the approaches used to overcome these issues is the preparation of solid dispersions. In this study, thermal analysis and pyrolysis coupled with gas chromatography-mass spectrometry (GC/MS) were employed to determine efavirenz thermal stability and the solid dispersion with poly (vinylpyrrolidone-co-vinylacetate) (PVPVA 64). Thus, it suggests that EFZ was converted to its amorphous state, and there was an increase in EFZ thermal stability when it is dispersed in a polymer matrix compared to the drug alone, since there was an increase in the activation Energy (Ea) and a decrease in frequency factor (A). Furthermore, there was a change in the zero reaction order to one. The thermal stability time of the formulation was estimated at 7 months. In addition, it was possible to observe a good correlation between loss of mass and the technique of Pyrolysis-GC–MS and to posit the formation of new fragments, which clarifies the technique with regard to the identification of thermal decomposition fragments.

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Acknowledgements

The authors would like to thank the Improving Coordination for Senior Staff (CAPES) and National Council of Scientific and Technological Development (CNPq) for financial support, Pharmaceutical Laboratory in the State of Pernambuco (LAFEPE) and the University of Toronto for the donation of raw materials and the Department of Pharmaceutical Sciences of the Federal University of Paraíba for performing the Pyrolysis-GC/MS analyses and DSC photo-visuals.

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Authors and Affiliations

  1. Laboratory of Nanotechnology and Nanomedicine - Institute of Technology and Research, Universidade Tiradentes, Murilo Dantas Avenue, 300, Farolândia, Aracaju, SE, 49.032-490, Brazil

    Salvana Priscylla Manso Costa

  2. Laboratory of Medicine Technology - Department of Pharmaceutical Sciences, Federal University of Pernambuco, Professor Arthur de Sá Street, s/n, Cidade Universitária, Recife, PE, 50740-521, Brazil

    Tarcyla de Andrade Gomes, Paulo Cezar Dantas da Silva, Adriana Eun He Koo Yun, Rosali Maria Ferreira da Silva & Pedro José Rolim Neto

  3. Institute of Exact Sciences and Technology, Federal University of Amazonas, Nossa Senhora do Rosário Street, 3863, Tiradentes, Itacoatiara, AM, Brazil

    Keyla Emanuelle Ramos da Silva

  4. Unified Drug Development and Testing Laboratories - Department of Pharmaceutical Sciences, Federal University of Paraíba, Campus I, João Pessoa, PB, 58059-900, Brazil

    Taynara Batista Lins Melo, Fabrício Havy Dantas de Andrade & Fabio Souza Santos

  5. Analytical Center – College of Pharmaceutical Sciences, Federal University of Vale do São Francisco, José de Sá Maniçoba Avenue, s/n, Centro, Petrolina, PE, 56304-917, Brazil

    Larissa Araújo Rolim

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  1. Salvana Priscylla Manso Costa
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Costa, S.P.M., de Andrade Gomes, T., da Silva, K.E.R. et al. Characterization and thermal stability study of efavirenz and solid dispersion with PVPVA 64 by means of thermal analysis and pyrolysis coupled with GC/MS. J Therm Anal Calorim 146, 2169–2182 (2021). https://doi.org/10.1007/s10973-020-10350-5

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