Estudo da formação de cocristais, misturas físicas e eutéticos por síntese mecanoquímica dos princípios ativos curcumina e norfloxacino com alguns coformadores selecionados
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Data
2019-02-22
Autores
Ferreira, Laura Teófilo
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Universidade Estadual Paulista (Unesp)
Resumo
Cocristais farmacêuticos podem ser definidos como sólidos cristalinos multicomponentes (dois ou mais componentes), sendo estes um API (do inglês “active pharmaceutical ingredients”, ou seja, uma molécula com atividade farmacológica) e um coformador, os quais são unidos por interações não covalentes, mais comumente ligações de hidrogênio. O coformador deve ser uma molécula segura para consumo (uma vitaminas, um antioxidantes ou outro API, por exemplo) e deve conter grupos funcionais que possibilitem a interação com o API. Os cocristais são um artificio eficiente para solucionar problemas de solubilidade encontrados nos fármacos classes II e IV (segundo o Sistema de Classificação Biofarmacêutica). O método mecanoquímico permite reprodutibilidade na síntese dos cocristais. Neste trabalho realizou-se a síntese mecanoquímica do API Curcumina com os coformadores ácido ascórbico, ácido cítrico, cafeína e sacarina, e do API Norfloxacino com os coformadores riboflavina, ácido salicílico e acido succínico. Observou-se que a riboflavina apresenta comportamento térmico diferente do relatado na literatura, mostrando inicialmente uma etapa de decomposição térmica, seguido de um evento endotérmico referente à fusão, eventos confirmados por imagens do DSC-Fotovisual. O Norfloxacino sofre influencia pelo processo de moagem, a qual induz a transferência de prótons e interação do composto com moléculas de água, condição característica do norfloxacino, já relatado na literatura. O Norfloxacino formou cocristais com os coformadores riboflavina, ácido salicílico e ácido succínico, todos nas proporções 1:1, por método mecanoquímico, moagem assistida por solvente, utilizando 15 uL de solvente clorofórmio. A Curcumina não formou cocristais com os coformadores estudados, no entanto a Curcumina formou misturas físicas com o coformador ácido ascórbico, compostos eutéticos com excesso de reagentes com o coformador sacarina, assim como para o coformador cafeína, e misturas físicas e um composto eutético como o coformador ácido cítrico, todos por método mecanoquímico, utilizando 15 uL de solvente etanol.
Pharmaceutical cocrystals can be defined as multicomponent crystalline solids (two or more components), these being an active pharmaceutical ingredients (API) and a coformer, which are joined by non-covalent interactions, most commonly hydrogen bonds. The coformer must be a safe molecule for consumption and must contain functional groups that allow interaction with the API. Cocrystals are an efficient device for solving solubility problems found in Class II and IV drugs (according to the Biopharmaceutical Classification System). The mechanochemical method allows reproducibility in the synthesis of cocrystals. In this work the mechanochemical synthesis of API Curcumina with the ascorbic acid, citric acid, caffeine and saccharin coformers and the Norfloxacino API with riboflavin, salicylic acid and succinic acid coformers were performed. It was observed that riboflavin exhibits thermal behavior different from that reported in the literature, initially showing a thermal decomposition stage, followed by an endothermic event related to the fusion, events confirmed by DSC-Photovisual images. Norfloxacin is influenced by the milling process, which induces the proton transfer and interaction of the compound with water molecules, a characteristic condition of norfloxacin, already reported in the literature. Norfloxacin formed cocrystals with the riboflavin, salicylic acid and succinic acid coformers, all in 1:1 proportions by mechanochemical method, solvent-assisted grinding using 15 uL of chloroform solvent. Curcumin did not form cocrystals with the coformers studied, however curcumin formed physical mixtures with the ascorbic acid coformator, eutectic compounds with excess reagents with the saccharin coformer, as well as the caffeine coformer, and physical mixtures and a eutectic compound such as citric acid coformer, all by mechanochemical method using 15 uL of solvent ethanol.
Pharmaceutical cocrystals can be defined as multicomponent crystalline solids (two or more components), these being an active pharmaceutical ingredients (API) and a coformer, which are joined by non-covalent interactions, most commonly hydrogen bonds. The coformer must be a safe molecule for consumption and must contain functional groups that allow interaction with the API. Cocrystals are an efficient device for solving solubility problems found in Class II and IV drugs (according to the Biopharmaceutical Classification System). The mechanochemical method allows reproducibility in the synthesis of cocrystals. In this work the mechanochemical synthesis of API Curcumina with the ascorbic acid, citric acid, caffeine and saccharin coformers and the Norfloxacino API with riboflavin, salicylic acid and succinic acid coformers were performed. It was observed that riboflavin exhibits thermal behavior different from that reported in the literature, initially showing a thermal decomposition stage, followed by an endothermic event related to the fusion, events confirmed by DSC-Photovisual images. Norfloxacin is influenced by the milling process, which induces the proton transfer and interaction of the compound with water molecules, a characteristic condition of norfloxacin, already reported in the literature. Norfloxacin formed cocrystals with the riboflavin, salicylic acid and succinic acid coformers, all in 1:1 proportions by mechanochemical method, solvent-assisted grinding using 15 uL of chloroform solvent. Curcumin did not form cocrystals with the coformers studied, however curcumin formed physical mixtures with the ascorbic acid coformator, eutectic compounds with excess reagents with the saccharin coformer, as well as the caffeine coformer, and physical mixtures and a eutectic compound such as citric acid coformer, all by mechanochemical method using 15 uL of solvent ethanol.
Descrição
Palavras-chave
Norfloxacino, Curcumina, Cocristais, Mecanoquímica, Análise térmica, Norfloxacin, Curcumin, Cocrystal, Mecanochemistry, Thermal analysis