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Ketoconazole: compatibility with pharmaceutical excipients using DSC and TG techniques

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Abstract

Ketoconazole (KTZ) is an antifungal agent responsible for the inhibition of 14-α-demethylase sterol. The drug–excipient compatibility studies play an important role in pharmaceutical formulations development. Interactions between drug and excipients may affect the chemical nature, stability, bioavailability and consequently the therapeutic efficacy and safety profile. The main goal of this work was to evaluate the compatibility of KTZ with some excipients: corn starch, microcrystalline cellulose, colloidal silicon dioxide, lactose monohydrate and povidone, using differential scanning calorimetry and thermogravimetry (TG). Binary mixtures in a mass ratio of 1:1 between drug and excipient were used to make the study feasible. The comparison was performed using Tonset of the melt from pure drug and its enthalpy value (ΔHf) with respective values obtained for each binary mixture. Experimental and simulated TG/DTG curves were compared using the Pearson’s correlation coefficients to assess possible incompatibilities due to thermal decomposition of organic matter and/or gaseous products released. Thus, the excipients corn starch and colloidal silicon dioxide have been shown to be incompatible with KTZ.

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Acknowledgements

The authors would like to thank FAPEMIG, Capes (Case No. 1739641) and CNPq for funding (Grant No. CAG).

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Authors and Affiliations

  1. LACFar, Institute of Chemistry, Federal University of Alfenas (UNIFAL-MG), Alfenas, Minas Gerais, 37130-000, Brazil

    Mariana S. Lopes, Tiago A. Catelani, André L. C. S. Nascimento, Jerusa S. Garcia & Marcello G. Trevisan

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  1. Mariana S. Lopes
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  2. Tiago A. Catelani
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  3. André L. C. S. Nascimento
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  4. Jerusa S. Garcia
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  5. Marcello G. Trevisan
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Correspondence to Marcello G. Trevisan.

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Fig. S1

Correlation graphs of the blends with (a) microcrystalline cellulose, (b) colloidal silicon dioxide, (c) povidone, (d) lactose monohydrate, (e) corn starch. (TIFF 3805 kb)

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Lopes, M.S., Catelani, T.A., Nascimento, A.L.C.S. et al. Ketoconazole: compatibility with pharmaceutical excipients using DSC and TG techniques. J Therm Anal Calorim 141, 1371–1378 (2020). https://doi.org/10.1007/s10973-019-09137-0

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  • DOI: https://doi.org/10.1007/s10973-019-09137-0

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