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

Autor(es)

da Silva, Cecilia C. P. ^{[1, 2]} ; de Melo, Cristiane C. ^{[1, 3]} ; Souza, Matheus S. ^[1] ; Diniz, Luan F. ^[1] ; Carneiro, Renato L. ^[2] ; Ellena, Javier ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Inst Fis Sao Carlos, BR-13560970 Sao Carlos, SP - Brazil

^[2] Univ Fed Sao Carlos, Dept Quim, BR-13083887 Sao Carlos, SP - Brazil

^[3] Univ Fed Alfenas, Fac Ciencias Farmaceut, BR-37130000 Alfenas, MG - Brazil

• Tipo de documento: Artigo Científico
• Fonte: JOURNAL OF PHARMACEUTICAL INNOVATION; v. 14, n. 1, p. 50-56, MAR 2019.
• Citações Web of Science: 2

Resumo

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. 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. 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. 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. (AU)

• Processo FAPESP: 15/25694-0 - Obtenção, caracterização e avaliação de novas formas sólidas cristalinas de fármacos usados no tratamento da tuberculose
• Beneficiário: Luan Farinelli Diniz
• Modalidade de apoio: Bolsas no Brasil - Mestrado