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Mechanochemical synthesis, thermoanalytical study and characterization of new multicomponent solid forms of norfloxacin with saccharin

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Abstract

Cocrystallization is a very efficient strategy to improve the physicochemical properties of bioactive agents. A new norfloxacin (NOR)–saccharin cocrystal and a cocrystal–solvate were synthesized through the mechanochemical method (neat and liquid-assisted grinding), and the characterization was performed by thermal analysis (TG–DTA, DSC and DSC microscopy), infrared vibrational spectroscopy and powder X-ray diffraction. Moreover, solubility experiments carried out in water and buffer solutions (pH 3.0, 6.1 and 8.5) showed that norfloxacin has an aqueous solubility 3.5 times higher when cocrystallized with saccharin than in its pristine state, and an inverted pH-dependency compared to NOR alone (2 times higher in 6.1, slightly increase in pH 3.0, and a decrease of 0.7 times in 8.5 buffer solution). Furthermore, the solvate–cocrystal has a water solubility 2.3 times higher than NOR and the same solubility in 6.1 buffer solution than the cocrystal (2 times higher than NOR alone).

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Acknowledgements

The authors thank CPID/CDMF, FAPESP (Grant Nos. 2013/09022-7, 2017/14936-9, 2018/12463-9 and 2018/24378-6), CNPq (Grant Nos. 421469/2016-1and 159936/2018-7) and CAPES (Grant No. 001) foundations (Brazil) for financial support.

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Authors and Affiliations

  1. São Paulo State University (UNESP), Institute of Chemistry, Araraquara, SP, Brazil

    Patrícia Osório Ferreira & Flávio Junior Caires

  2. School of Science, Chemistry Department, São Paulo State University (UNESP), Bauru, SP, Brazil

    Patrícia Osório Ferreira, Aniele de Moura, Amanda Cosmo de Almeida, Éverton Carvalho dos Santos & Flávio Junior Caires

  3. Federal University of Goias (UFG), School of Pharmacy, Goiania, GO, Brazil

    Ana Carolina Kogawa

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  1. Patrícia Osório Ferreira
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Ferreira, P.O., de Moura, A., de Almeida, A.C. et al. Mechanochemical synthesis, thermoanalytical study and characterization of new multicomponent solid forms of norfloxacin with saccharin. J Therm Anal Calorim 147, 1985–1997 (2022). https://doi.org/10.1007/s10973-021-10658-w

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