Mechanochemical synthesis of a multicomponent solid form: the case of 5-fluorocytosine isoniazid codrug.
SOUZA, Matheus S.; DINIZ, Luan F.; VOGT, Lautaro; CARVALHO JR., Paulo S.; D' VRIES, Richard F.; ELLENA, Javier.
SOUZA, Matheus S.; DINIZ, Luan F.; VOGT, Lautaro; CARVALHO JR., Paulo S.; D' VRIES, Richard F.; ELLENA, Javier.
 Abstract: Mechanochemistry synthesis was applied to the supramolecular synthesis and green scale-up production of a 1:1 drug-drug cocrystal involving the antimetabolite prodrug 5-Fluorocytosine (5-FC) and the tuberculostatic drug Isoniazid (INH), namely, 5FC-INH. Crystalline material, also obtained by traditional slow evaporation methods, was analyzed by single-crystal X-ray diffraction (XRD). The crystal packing is stabilized by a classical N-H···N hydrogen-bond interaction between the amine moiety of 5-FC and the INH pyridine nitrogen. IR and Raman data provided spectroscopic evidence about the hydrogen atom positions, thereby confirming the neutral nature of the cocrystal. Furthermore, 5FC-INH codrug was also evaluated by a range of analytical techniques such as powder XRD and thermal (thermogravimetric analysis, differential scanning calorimetry, hot stage microscopy) analyses. A physical stability study was performed in high relative humidity conditions to verify possible 5-FC solid-state hydration and/or INH degradation. The equilibrium solubility of this codrug was compared to the anhydrous 5-FC and INH raw materials, in pH 1.2 buffer media, and it was found to be similar to that of 5-FC, a biopharmaceutics classification system class I drug. The results show that the cocrystal has superior phase stability properties against moisture when compared to the starting pharmaceutical ingredients, so it could be considered as a potential candidate for the treatment of concomitant fungal infections, tuberculosis, and cancer. | |
| Crystal Growth and Design |
| v. 18, n. 9, p. 5202-5209 - Ano: 2018 |
| Fator de Impacto: 3,972 |
| http://dx.doi.org/10.1021/acs.cgd.8b00647 |  @article={002904086,author = {SOUZA, Matheus S.; DINIZ, Luan F.; VOGT, Lautaro; CARVALHO JR., Paulo S.; D' VRIES, Richard F.; ELLENA, Javier.},title={Mechanochemical synthesis of a multicomponent solid form: the case of 5-fluorocytosine isoniazid codrug},journal={Crystal Growth and Design},note={v. 18, n. 9, p. 5202-5209},year={2018}} |