Determinação do equilíbrio sólido-líquido de princípios ativos farmacêuticos

• Autor(a) principal: Assis, Gabriel Pereira
• Data de Publicação: 2021
• Tipo de documento: Dissertação
• Idioma: por
• Título da fonte: Repositório Institucional da UFSCAR
• Texto Completo: https://repositorio.ufscar.br/handle/ufscar/13984
• topic: Equilíbrio sólido-líquido; Solubilidade; Paracetamol; Nicotinamida; Cristalização; Modelos termodinâmicos; Solid-liquid equilibrium; Solubility; Nicotinamide; Crystallization; Thermodynamics models; ENGENHARIAS::ENGENHARIA QUIMICA::PROCESSOS INDUSTRIAIS DE ENGENHARIA QUIMICA

Solubility is one of most important property to produce active pharmaceutical ingredients (APIs), beyond of being related to its bioavailability. In this context, it was determined paracetamol and nicotinamide solid-liquid equilibrium in temperatures from 20 to 50°C for two solvent systems: water - ethanol and water- propylene glycol (PG), by refractometry method and the crystals formed were characterized by optical microcopy (OM), scanning electron microscopy (SEM) and X-ray Diffraction (XRD). The experimental results were compared with five thermodynamic models (Apelblat, Wilson, UNIQUAC, NRTL and λh) and data from the literature, showing good correlations among the correlative models for Apelblat in all cases among the activity coefficient models, the best adjustment, in all cases, were the NRTL model with the solvent-solvent parameters determined on this work. For water-ethanol-paracetamol system were observed maximum values of solubility with composition of 75% w/w of ethanol, which is not usual, but presented on previous works from literature, not occurring with PG. For water-PG-nicotinamide system was observed a point of local maximum on 25% w/w concentration and a point of local minimum on 75% w/w concentration. Beside that the temperatures of 20ºC and 25ºC showed a distinguished comportment compered to temperatures between 30ºC and 50ºC. The solubility curves on water-ethanol-nicotinamide system showed differences among the temperatures evaluated. The experimental data of nicotinamide solubility in pure water and pure ethanol showed similarity with literature data validating the methodology used and the water-PG system data. X-ray diffraction measurements on the crystals of paracetamol in equilibrium with the liquid indicate that maximum solubility is not associated with a change in the crystalline structure of the solid; optical microscopy of nicotinamide crystals indicated a possible change in the crystalline habit. X-ray diffraction of nicotinamide indicate a possible change in the crystalline structure or a possible preferred orientation, been necessary more studies.