| Full text | |
| Author(s): Show less - |
de Araujo, Gabriel L. B.
[1]
;
Ferreira, Fabio Furlan
[2]
;
Bernardes, Carlos E. S.
[3, 4]
;
Sato, Juliana A. P.
[2]
;
Gil, Otavio M.
[5]
;
de Faria, Dalva L. A.
[5]
;
Loebenberg, Raimar
[6]
;
Byrn, Stephen R.
[7]
;
Ghisleni, Daniela D. M.
[1]
;
Bou-Chacra, Nadia A.
[1]
;
Pinto, Terezinha J. A.
[1]
;
Antonio, Selma G.
[8]
;
Ferraz, Humberto G.
[1]
;
Zemlyanov, Dmitry
[9]
;
Goncalves, Debora S.
[1]
;
Minas da Piedade, Manuel E.
[3]
Total Authors: 16
|
| Affiliation: | [1] Univ Sao Paulo, Fac Ciencias Farmaceut, Dept Farm, Sao Paulo, SP - Brazil
[2] UFABC, Ctr Ciencias Nat & Humanas, Sao Paulo - Brazil
[3] Univ Lisbon, Fac Ciencias, Ctr Quim & Bioquim, P-1748016 Lisbon - Portugal
[4] Univ Lisbon, Fac Ciencias, Ctr Quim Estrutural, P-1748016 Lisbon - Portugal
[5] Univ Sao Paulo, Inst Quim, Dept Quim Fundamental, Sao Paulo, SP - Brazil
[6] Univ Alberta, Fac Pharm & Pharmaceut Sci, Edmonton, AB T6G 2H7 - Canada
[7] Purdue Univ, Dept Ind & Phys Pharm, W Lafayette, IN 47907 - USA
[8] Univ Estadual Paulista, Inst Quim, Dept Fis Quim, Araraquara - Brazil
[9] Purdue Univ, Birck Nanotechnol Ctr, W Lafayette, IN 47907 - USA
Total Affiliations: 9
|
| Document type: | Journal article |
| Source: | Crystal Growth & Design; v. 18, n. 4, p. 2377-2386, APR 2018. |
| Web of Science Citations: | 3 |
| Abstract | |
The use of flubendazole (FBZ) in the treatment of lymphatic filariasis and onchocerciasis (two high incidence neglected tropical diseases) has been hampered by its poor aqueous solubility. A material consisting of binary flubendazole/maleic acid crystals (FBZ/MA), showing considerably improved solubility and dissolution rate relative to flubendazole alone, has been prepared in this work through solvent assisted mechanical grinding. The identification of FBZ/MA as a binary crystalline compound with salt character (proton transfer from MA to FBZ) relied on the combined results of powder X-ray diffraction, Raman spectroscopy, attenuated total reflection Fourier transform infrared spectroscopy (ATR-FTIR), X-ray photoelectron spectroscopy (XPS), thermogravimetry (TG), and differential scanning calorimetry (DSC). Isothermal solution microcalorimetry studies further suggested that the direct formation of FBZ/MA from its precursors in the solid state is thermodynamically favored. A comparison of the in silico pharmacokinetic performance of the FBZ/MA with that of pure FBZ based on a rat fasted physiology model indicated that the absorption rate, mean plasma peak concentration, and absorption extension of FBZ/MA were similar to 2.6 times, similar to 1.4 times, and 60% larger, respectively, than those of FBZ. The results here obtained therefore suggest that the new FBZ/MA salt has a considerable potential for the development of stable and affordable pharmaceutical formulations with improved dissolution and pharmacokinetic properties. Finally, powder X-ray diffraction studies also led to the first determination of the crystal structure of FBZ. (AU) | |
| FAPESP's process: | 15/05685-7 - Crystallization and polymorphism of Flubendazole and other ill-characterized drugs |
| Grantee: | Gabriel Lima Barros de Araujo |
| Support Opportunities: | Regular Research Grants |
| FAPESP's process: | 15/26233-7 - Synthesis and structural characterization of cocrystals for application as sunscreen and antioxidants of topical use |
| Grantee: | Fabio Furlan Ferreira |
| Support Opportunities: | Regular Research Grants |