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Studying the thermal decomposition of carvedilol by coupled TG-FTIR

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Abstract

Thermal analytical behavior of carvedilol (1-(9H-carbazol-4-yloxy)-3-[[2-(2-methoxyphenoxy)ethyl]amine]-2-propanol), a β-blocker antihypertensive drug, has been investigated using thermoanalytical techniques thermogravimetry, derivative thermogravimetry, differential thermal analysis (DTA) and differential scanning calorimetry (DSC). Evolved gas analysis was also performed using thermogravimetry coupled to infrared spectroscopy. Such studies revealed that carvedilol decomposes after melting, releasing 2-methoxyphenol and ammonia in both nitrogen and air atmospheres. In inert atmosphere, the decomposition took place as a single mass loss event without residue at the end of the experiment, while in air, the first step resulted in carbonaceous residue that burnt completely in the second step. DTA and DSC curves demonstrated that the sample melts around 100 °C (ΔH fus = 126.6 J g−1, ΔS fus = 0.32 J K−1 g−1) without recrystallization on cooling. An endothermic event observed previously to the melt has been attributed to concomitant carvedilol forms in the sample. Solid-state decomposition kinetic investigation using the Flynn–Wall–Ozawa approach revealed activation energy of E a = 243 ± 32 kJ mol−1 and Arrhenius pre-exponential factor log A = 22 ± 3 min−1. Finally, a tentative mechanism for carvedilol thermal decomposition is proposed.

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Acknowledgements

Authors are grateful to the Brazilian Foundations Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), Fundação de Apoio à Pesquisa do Estado de São Paulo (FAPESP) and Núcleo de Pesquisa em Ciência e Tecnologia de Biorecursos (CiTecBio/NAPs-PRP/USP) by research grant and Santander-USP fellowship to RCG.

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Authors and Affiliations

  1. Departamento de Química e Física Molecular, Instituto de Química de São Carlos, USP, Av. Trabalhador São-Carlense, 400, Caixa Postal 780, São Carlos, São Paulo, CEP 13560-970, Brazil

    R. C. Gallo, A. P. G. Ferreira & E. T. G. Cavalheiro

  2. Faculty of Pharmacy, University of Coimbra, Coimbra, Portugal

    R. E. A. Castro

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  1. R. C. Gallo
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  2. A. P. G. Ferreira
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  3. R. E. A. Castro
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  4. E. T. G. Cavalheiro
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Correspondence to E. T. G. Cavalheiro.

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Gallo, R.C., Ferreira, A.P.G., Castro, R.E.A. et al. Studying the thermal decomposition of carvedilol by coupled TG-FTIR. J Therm Anal Calorim 123, 2307–2312 (2016). https://doi.org/10.1007/s10973-015-4931-3

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