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.
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}} |