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5-Fluorocytosine/5-Fluorouracil Drug-Drug Cocrystal: a New Development Route Based on Mechanochemical Synthesis

  • Cecilia C. P. da Silva
  • Cristiane C. de Melo
  • Matheus S. Souza
  • Luan F. Diniz
  • Renato L. Carneiro
  • Javier Ellena
Original Article
  • 23 Downloads

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.

Keywords

Mechanochemistry 5-Fluorocytosine 5-Fluorouracil Cocrystal Physical stability Solid-state characterization 

Notes

Funding information

The authors received financial support from CAPES (C.C.P.S. and M.S.S.), CNPq (C.C.M., J.E. grant #305190/2017-2), and FAPESP (L.F.D. grant #15/25694-0).

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Instituto de Física de São CarlosUniversidade de São PauloSão CarlosBrazil
  2. 2.Departamento de QuímicaUniversidade Federal de São CarlosSão CarlosBrazil
  3. 3.Faculdade de Ciências FarmacêuticasUniversidade Federal de AlfenasAlfenasBrazil

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