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5-fluorocytosine/5-fluorouracil drug-drug cocrystal: a new development route based on mechanochemical synthesis.
SILVA, Cecilia C. P.; MELO, Cristiane C.; SOUZA, Matheus S.; DINIZ, Luan F.; CARNEIRO, Renato L.; ELLENA, Javier.
Abstract: Purpose: Mechanochemistry is addressed here for the green formation of a 1:1 pharmaceutical cocrystal involving the antifungal prodrug 5-Fluorocytosine (5-FC) and the antineoplastic drug 5-Fluorouracil (5-FU). Crystalline material of this drug-drug cocrystal (DDC) was previously obtained by slow evaporation from solution (SES) and was then structurally analyzed. Method: In this paper, neat grinding and solvent-drop grinding (SDG) were applied in an attempt to achieve a route for the supramolecular synthesis of this cocrystal, exhibiting suitable yield and amount for solid characterization, which were not achieved via the SES method. Results: SDG provided the solid drug-drug cocrystal form. The resulting material had its physical stability monitored for 2 years and was then evaluated by a range of analytical technologies: X-ray powder diffraction, differential scanning calorimetry, hot-stage microscopy, thermogravimetric, and spectroscopic analysis. Conclusions: The new cocrystal proved to be stable for 6 months and in environments with high relative humidity. In this sense, it is believed that the new DDC is a potential model system which could be used as a base for further developments in the field, for other molecules or in relation to the feasibility of using this cocrystal therapeutically.
Journal of Pharmaceutical Innovation
v. 14, n. 1, p. 50-56 - Ano: 2019
Fator de Impacto: 1,934
http://dx.doi.org/10.1007/s12247-018-9333-1
    @article={002927997,author = {SILVA, Cecilia C. P.; MELO, Cristiane C.; SOUZA, Matheus S.; DINIZ, Luan F.; CARNEIRO, Renato L.; ELLENA, Javier.},title={5-fluorocytosine/5-fluorouracil drug-drug cocrystal: a new development route based on mechanochemical synthesis},journal={Journal of Pharmaceutical Innovation},note={v. 14, n. 1, p. 50-56},year={2019}}