Cecilia C. P. da Silva, Cristiane C. de Melo, Matheus S. Souza, Luan F. Diniz, Renato L. Carneiro, Javier Ellena,
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.
https://doi.org/10.1007/s12247-018-9333-1
@article{da_Silva_2018, doi = {10.1007/s12247-018-9333-1}, url = {https://doi.org/10.1007%2Fs12247-018-9333-1}, year = 2018, month = {jun}, publisher = {Springer Science and Business Media {LLC}}, volume = {14}, number = {1}, pages = {50--56}, author = {Cecilia C. P. da Silva and Cristiane C. de Melo and Matheus S. Souza and Luan F. Diniz and Renato L. Carneiro and Javier Ellena}, title = {5-Fluorocytosine/5-Fluorouracil Drug-Drug Cocrystal: a New Development Route Based on Mechanochemical Synthesis}, journal = {Journal of Pharmaceutical Innovation} }