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Mechanochemical Synthesis of a Multicomponent Solid Form: The Case of 5-Fluorocytosine Isoniazid Codrug
- Source :
- Crystal Growth & Design; August 2018, Vol. 18 Issue: 9 p5202-5209, 8p
- Publication Year :
- 2018
-
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.
Details
- Language :
- English
- ISSN :
- 15287483 and 15287505
- Volume :
- 18
- Issue :
- 9
- Database :
- Supplemental Index
- Journal :
- Crystal Growth & Design
- Publication Type :
- Periodical
- Accession number :
- ejs46022021
- Full Text :
- https://doi.org/10.1021/acs.cgd.8b00647