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Simultaneous measurements of X-ray diffraction–differential scanning calorimetry

The investigation of the phase transition of ganciclovir and characterization of its polymorphic forms

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Abstract

Ganciclovir (GCV) is an antiviral drug for treating cytomegalovirus infections. This drug is reported to exist in four crystal forms in the solid state, with I and II being anhydrous and III and IV hydrates. Of particular interest about its thermal behavior, we performed simultaneous measurements of X-ray diffraction and differential scanning calorimetry (DSC) from a GCV commercial sample. The results showed that GCV Form III was stable between room temperature and ± 180 °C, and it transformed to Form I around 189 °C. Furthermore, the crystallization studies by slow solvent evaporation led to four GCV polymorphic forms (Form I, III, IV, and V), one anhydrous and three hydrated, respectively. GCV crystal forms were characterized by X-ray powder diffraction, thermogravimetry/derivative thermogravimetry, DSC, Fourier transform infrared spectroscopy and elemental analysis. Notable differences in the peak positions, shapes and intensities were detected. Slurry conversion experiments found that all recrystallized forms of GCV converted to Form I over time, consistent with Form I being the thermodynamically stable form. These results are relevant for the pharmaceutical development of GCV.

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Acknowledgements

The authors thank Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) of Brazil (Project No 141395/2013-3) for financial supported. Roxana L. Roque-Flores thanks Eurofarma Pharmaceutical Company (Brazil) and Matheus Costa for the donation of the sample and use of the equipment hot-stage microscopy.

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Authors and Affiliations

  1. Departamento de Farmácia, Faculdade de Ciências Farmacêuticas, Universidade de São Paulo, Av. Prof. Lineu Prestes, 580, São Paulo, SP, 05508-000, Brazil

    Roxana Lili Roque-Flores

  2. Departamento de Química Fundamental, Instituto de Química, Universidade de São Paulo, Av. Prof. Lineu Prestes, 748, São Paulo, SP, 05508-000, Brazil

    Jivaldo do Rosário Matos

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  1. Roxana Lili Roque-Flores
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  2. Jivaldo do Rosário Matos
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Correspondence to Roxana Lili Roque-Flores.

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Roque-Flores, R.L., Matos, J.R. Simultaneous measurements of X-ray diffraction–differential scanning calorimetry. J Therm Anal Calorim 137, 1347–1358 (2019). https://doi.org/10.1007/s10973-019-08031-z

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  • DOI: https://doi.org/10.1007/s10973-019-08031-z

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