| Autor: |
Queiroz LHS; NUPFARQ, Programa de Pós-Graduação em Ciência dos Materiais (PPGCM), Centro de Ciências de Imperatriz (CCIM), Universidade Federal do Maranhão (UFMA), Imperatriz, Maranhão 65.900-410, Brazil., Barros RS; NUPFARQ, Programa de Pós-Graduação em Ciência dos Materiais (PPGCM), Centro de Ciências de Imperatriz (CCIM), Universidade Federal do Maranhão (UFMA), Imperatriz, Maranhão 65.900-410, Brazil., de Sousa FF; Instituto de Ciências Exatas e Naturais, Universidade Federal do Pará (UFPA), Belém, Pará 65.075-110, Brazil., Lage MR; NUPFARQ, Programa de Pós-Graduação em Ciência dos Materiais (PPGCM), Centro de Ciências de Imperatriz (CCIM), Universidade Federal do Maranhão (UFMA), Imperatriz, Maranhão 65.900-410, Brazil.; Coordenação do Curso de Ciência e Tecnologia, Centro de Ciências de Balsas, Universidade Federal do Maranhão (UFMA), Balsas, Maranhão 65.800-000, Brazil., Sarraguça MC; LAQV, REQUIMTE, Department of Chemical Sciences, Laboratory of Applied Chemistry, Faculty of Pharmacy, Porto University, Rua de Jorge Viterbo Ferreira, 228, Porto 4050-313, Portugal., Ribeiro PRS; NUPFARQ, Programa de Pós-Graduação em Ciência dos Materiais (PPGCM), Centro de Ciências de Imperatriz (CCIM), Universidade Federal do Maranhão (UFMA), Imperatriz, Maranhão 65.900-410, Brazil. |
| Abstrakt: |
Rifampicin (RIF) is an antibiotic used to treat tuberculosis and leprosy. Even though RIF is a market-available drug, it has a low aqueous solubility, hindering its bioavailability. Among the strategies for bioavailability improvement of poorly soluble drugs, coamorphous systems have been revealed as an alternative in the increase of the aqueous solubility of drug systems and at the same time also increasing the amorphous state stability and dissolution rate when compared with the neat drug. In this work, a new coamorphous form from RIF and tromethamine (TRIS) was synthesized by slow evaporation. Structural, electronic, and thermodynamic properties and solvation effects, as well as drug-coformer intermolecular interactions, were studied through density functional theory (DFT) calculations. Powder X-ray diffraction (PXRD) data allowed us to verify the formation of a new coamorphous. In addition, the DFT study indicates a possible intermolecular interaction by hydrogen bonds between the available amino and carbonyl groups of RIF and the hydroxyl and amino groups of TRIS. The theoretical spectra obtained are in good agreement with the experimental data, suggesting the main interactions occurring in the formation of the coamorphous system. PXRD was used to study the physical stability of the coamorphous system under accelerated ICH conditions (40 °C and 75% RH), indicating that the material remained in an amorphous state up to 180 days. The thermogravimetry result of this material showed a good thermal stability up to 153 °C, and differential scanning calorimetry showed that the glass temperature ( T g ) was at 70.0 °C. Solubility studies demonstrated an increase in the solubility of RIF by 5.5-fold when compared with its crystalline counterpart. Therefore, this new material presents critical parameters that can be considered in the development of new coamorphous formulations. |
