Emulsificação do fluconazol utilizando líquidos iônicos com cátions imidazolíneos e com contraíons carboxilatos

• Ano de defesa: 2024
• Autor(a) principal: Zibetti, Letícia
• Tipo de documento: Dissertação
• Tipo de acesso: Acesso aberto
• dARK ID: ark:/26339/0013000018wt5
• Idioma: por
• Instituição de defesa: Universidade Federal de Santa Maria; Brasil; Química; UFSM; Programa de Pós-Graduação em Química; Centro de Ciências Naturais e Exatas
• Palavras-chave em Português: Emulsão; Líquidos iônicos; Fluconazol; Emulsions; Ionic liquids; Fluconazole; CNPQ::CIENCIAS EXATAS E DA TERRA::QUIMICA
• Link de acesso: http://repositorio.ufsm.br/handle/1/32114

Fluconazole is a triazole class drug prescribed for the treatment of superficial and systemic fungal infections, which posses a broad spectrum of action. However, this drug presents many possibilities for drug interactions, which affects its bioavailability, and it has limited solubility, which makes it difficult to prepare pharmaceutical formulations. Preparing emulsions containing fluconazole could be a strategy to overcome these limitations. Amphiphilic imidazolinium-based ionic liquids (ILs) with long alkyl chains (≥ 8) have potential application as surfactants and can act as tensoactives in emulsions. However, the ability of ILs to act as unique emulsifiers and in the emulsification of fluconazole is little explored. Amphiphilic ILs also have outstanding antibacterial and antifungal activity, but ILs with long alkyl chains (C > 12) and halogen-derived anions show considerable toxicity. Thus, with a view to using ILs as unique surfactants in nanoemulsions, the aim of this work was to prepare fluconazole emulsions using ILs derived from imidazole. To avoid the possible toxicity of the formulations, the selected ILs have a twelve-carbon alkyl chain and carboxylates (acetate – [C12MIM][Ace] and phenylalaninate – [C12MIM][Phe]) as counterions. Properties such as particle size, polydispersity index, morphology, encapsulation efficiency, viscosity, zeta potential and release kinetics were evaluated. The method of preparation, by ultrasound (US) and/or ultra-turrax (TU) and the concentration of the oil phase were investigated. The results showed that the ILs were synthesized with excellent yields (82 - 93 %). Thermogravimetric analysis showed the high thermal stability of the ILs (between 187 and 220 ºC) and differential scanning calorimetry analysis showed that [C12MIM][Phe] is an amorphous solid, while [C12MIM][Ace] is a crystalline solid. The ILs showed good solubility in water and ethanol, which is essential for pharmacological purposes. The density of the ILs increased as the molecular mass of the anions increased. In addition, the preparation of emulsions was successful and uniform droplets were observed. The emulsions prepared using US had a smaller particle size, greater homogeneity and stability and a lower polydispersity index. The viscosity results showed that the emulsions had viscosities close to that of water and that they all showed pseudoplastic behavior. The zeta potential value for emulsions containing [C12MIM][Phe] and [C12MIM][Ace] was positive, while for emulsions with LI [C12MIM][Br], this value was negative. The emulsions showed good encapsulation efficiency (≥ 67 %), showing that the systems have potential for encapsulating hydrophobic drugs. The release percentage of fluconazole was between 84 % and 95 % and the burst effect was observed. Atomic force microscopy and transmission electron microscopy showed that the emulsions had spherical particle shapes and confirmed the nanometric range (≤ 500 nm) of the particles. US was an efficient method for preparing stable fluconazole emulsions using more biocompatible ILs. The absence of an additional surfactant reinforced the potential of these ILs as unique emulsifying agents.