Mechanochemical Synthesis of a Multicomponent Solid Form: The Case of 5-Fluorocytosine Isoniazid Codrug
| dc.contributor.author | Souza, Matheus S. | |
| dc.contributor.author | Diniz, Luan F. | |
| dc.contributor.author | Vogt, Lautaro | |
| dc.contributor.author | Carvalho Jr., Paulo S. | |
| dc.contributor.author | D’vries, Richard F. | |
| dc.contributor.author | Ellena, Javier | |
| dc.date.accessioned | 2020-02-10T04:54:45Z | |
| dc.date.available | 2020-02-10T04:54:45Z | |
| dc.date.issued | 2018-07-12 | |
| dc.description.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. | es |
| dc.identifier.issn | 15287483 | |
| dc.identifier.uri | https://repositorio.usc.edu.co/handle/20.500.12421/2705 | |
| dc.language.iso | en | es |
| dc.publisher | American Chemical Society | es |
| dc.subject | Atoms | es |
| dc.subject | Crystalline materials | es |
| dc.subject | Hydrogen bonds | es |
| dc.subject | Single crystals | es |
| dc.subject | Stability | es |
| dc.subject | X ray diffraction | es |
| dc.title | Mechanochemical Synthesis of a Multicomponent Solid Form: The Case of 5-Fluorocytosine Isoniazid Codrug | es |
| dc.type | Article | es |
Files
Original bundle
1 - 1 of 1
No Thumbnail Available
- Name:
- Mechanochemical Synthesis of a Multicomponent Solid Form.jpg
- Size:
- 107.07 KB
- Format:
- Joint Photographic Experts Group/JPEG File Interchange Format (JFIF)
- Description:
License bundle
1 - 1 of 1
No Thumbnail Available
- Name:
- license.txt
- Size:
- 1.71 KB
- Format:
- Item-specific license agreed upon to submission
- Description: