Síntese mecanoquímica e caracterização de cocristal, coamorfos e misturas eutéticas de Valsartana
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Data
2021-10-26
Autores
Torquetti, Carolina
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Universidade Estadual Paulista (Unesp)
Resumo
O presente trabalho descreve a síntese e caracterização de novas formas sólidas farmacêuticas de valsartana com alguns coformadores (ácido 2-picolínico, picolinamida, cafeína e N-metil-D-glucamina) visando a melhora na solubilidade desse fármaco. Após estudo dos precursores, foi realizada a síntese mecanoquímica, que consistiu na moagem do fármaco juntamente com os coformadores em um moinho de bolas, assistida por solvente etanol, na proporção de 1:1. As formas sólidas multicomponentes sintetizadas foram caraterizadas através de análise termogravimétrica e análise térmica diferencial simultâneas (TGA-DTA), calorimetria exploratória diferencial (DSC), difratometria de raios X pelo método em pó (DRXP) e espectroscopia vibracional na região do infravermelho (IV). Também foi realizado o estudo através do diagrama de fases binário (frações molares de 0, 0,2, 0,3, 0,4, 0,5, 0,6, 0,7, 0,8 e 1) e estudo de variação do tempo de moagem e quantidade de solvente, quando necessário. Foram obtidas 2 misturas eutéticas (VAL-CAF/15 Hz e VAL-PCA/ 15 Hz), 2 coamorfos (VAL-PCA/ 30 Hz e VAL-NMDG/ 15Hz) e 1 cocristal (VAL-PA/ 15 Hz), todos promissores para futuros estudos de solubilidade e taxa de dissolução.
The present work present the synthesis and characterization of new solid pharmaceutical forms of valsartan with some coformers (2-picolinic acid, picolinamide, caffeine and N-methylD-glucamine) increases the improvement in the solubility of this drug. After studying the precursors, a synthesis was performed, which consisted of grinding the drug together with the coformers in a ball mill (mechanochemical method), assisted by ethanol, in a ratio of 1:1. The solid forms synthesized were studied through simultaneous thermogravimetric and differential thermal analysis (TGA-DTA), differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD) and vibrational spectroscopy in the infrared region (IV). The study was also carried out through the binary phase diagram (molar fractions of 0, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8 and 1) and a study of variation of grinding time and amount of solvent, when necessary. Two eutectic mixtures (VAL-CAF and VAL-PCA 15 Hz), 2 coamorphous (VAL-PCA 30 Hz and VAL-NMDG) and 1 cocrystal (VAL-PA) we displaced, all enabled for future studies of solubility and dissolution rate.
The present work present the synthesis and characterization of new solid pharmaceutical forms of valsartan with some coformers (2-picolinic acid, picolinamide, caffeine and N-methylD-glucamine) increases the improvement in the solubility of this drug. After studying the precursors, a synthesis was performed, which consisted of grinding the drug together with the coformers in a ball mill (mechanochemical method), assisted by ethanol, in a ratio of 1:1. The solid forms synthesized were studied through simultaneous thermogravimetric and differential thermal analysis (TGA-DTA), differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD) and vibrational spectroscopy in the infrared region (IV). The study was also carried out through the binary phase diagram (molar fractions of 0, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8 and 1) and a study of variation of grinding time and amount of solvent, when necessary. Two eutectic mixtures (VAL-CAF and VAL-PCA 15 Hz), 2 coamorphous (VAL-PCA 30 Hz and VAL-NMDG) and 1 cocrystal (VAL-PA) we displaced, all enabled for future studies of solubility and dissolution rate.
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Palavras-chave
Valsartana, Cocristal, Coamorfo, Mistura eutética, Análise térmica, Valsartan, Cocrystal, Coamorph, Eutectic mixture, Thermal analysis