Síntese e caracterização de líquidos iônicos baseados em monoetanolamina e colina e aplicação na cristalização do fármaco isoniazida

Detalhes bibliográficos
Ano de defesa: 2021
Autor(a) principal: Reis, Carla Luzia Borges
Orientador(a): Não Informado pela instituição
Banca de defesa: Não Informado pela instituição
Tipo de documento: Tese
Tipo de acesso: Acesso aberto
Idioma: por
Instituição de defesa: Não Informado pela instituição
Programa de Pós-Graduação: Não Informado pela instituição
Departamento: Não Informado pela instituição
País: Não Informado pela instituição
Palavras-chave em Português:
Link de acesso: http://www.repositorio.ufc.br/handle/riufc/64329
Resumo: The ionic liquids (ILs) are considered an attractive alternative to improve processes with economic, ecological purposes and can offer a new perspective on the crystallization of active pharmaceutical ingredients (APIs), due to the infinity of possibilities of ILs syntheses. In this context, the application of ILs in the crystallization of isoniazid (INH), one of the most used and important drugs in the treatment of tuberculosis, was studied, with the purpose of analyzing the effects on the characteristics of the drug, as well as the interaction with the ILs, synthesis of new compounds and manipulation of the crystalline habit. Initially, five ILs based on the choline cation with sulfuric, acetic, benzoic and citric acid were synthesized and characterized, as well as two ILs based on the monoethanolamine cation with acetic and formic acid. Subsequently, the seven ILs obtained were characterized by physical-chemical properties and used in the crystallization of INH by the solvent evaporation method. The acute toxicity tests against the microcrustacean Artemia salina showed that (2-hydroxyethyl)-trimethylammonium hydroxide; 2- hydroxyl ethylammonium formate and 2- hydroxyl ethylammonium acetate ILs did not show toxicity against the microcrustacean A. salina, while the (2-hydroxyethyl)-trimethylammonium acetate, (2-hydroxyethyl)-trimethylammonium bisulfate and (2-hydroxyethyl)-trimethylammonium citrate ILs showed low toxicity, with values of LD50 of de 529; 408 e 410 µg/mL. In the characterization of the new forms of INH, it was verified that the morphology and stability of the INH can be manipulated according to the chosen IL, producing habits different from those found in the crystallization with the precursor acids of the ILs. The INH:[ChOH] and INH:[ChCit] forms showed a powdery appearance, low solubility and in relation to the antimycobacterial action against Mycobacterium tuberculosis, they presented a minimum inhibitory concentration value of 100 and 12.5 µg/mL, respectively. The (2-hydroxyethyl)-trimethylammonium bisulfate IL caused a conformational change in the structure of isoniazid, led to the formation the 2-(4-pyridiniumcarbonyl)-hydrazine sulfate, with a solubility in water at 25 °C of 155.90 mg/mL, being improved compared to INH (137.90 mg/mL) under the same conditions. Therefore, the obtaining new solid forms of the drug INH in ILs, as well as the characterization and elucidation of its structure after crystallization, becomes innovative and it is considered an initial step for the use of new solvents in the crystallization of drugs.