A talidomida é um composto racêmico derivado do ácido glutâmico. A talidomida é aprovada para o tratamento das manifestações agudas cutâneas de eritema nodoso hansênico ou prevenção de recorrências (tipo II), para o tratamento de úlceras aftosas, mieloma múltiplo e doenças crônico degenerativas (como a doença do enxerto contra hospedeiro e lúpus). Em várias dessas condições, a administração intravenosa da talidomida seria vantajosa, porém, a talidomida possui limitações que dificultam sua administração por essa via, tais como a baixa solubilidade em água e hidrólise dependente do pH. Neste contexto, nanoemulsões aparecem como uma alternativa farmacoténica passível de alcançar este propósito. Este estudo teve como objetivo desenvolver nanoemulsões destinadas à administração intravenosa de talidomida. Na primeira parte do estudo, foi desenvolvido e validado um método por cromatografia líquida de alta eficiência, a fim de determinar o conteúdo de fármaco e de monitorar sua estabilidade nas formulações desenvolvidas. O método mostrou-se específico, linear (r2 > 0,9998), preciso (R.S.D. 0.9998), precise (RSD <1.33 %), accurate (recovery varied from 99.8-100.3 %) and robust. In the second part, different formulations were prepared using the method of spontaneous emulsification. The initial formulation for this study consisted by castor oil (10 %, w/w), soybean lecithin (3 %, w/w) and osmotic agent (glycerol, 2.5 %, w/w). Firstly, the optimization of the thalidomide amount to be incorporated was performed (0.1-0.5 mg/g). From the results of physical appearance, droplet size, zeta potential and drug content during the 60 days of storage, it was concluded that the best formulation, that is, those which presented the best characteristics was that contained 0.1 mg/g of thalidomide. The higher content formulations resulted in drug precipitation after 7 days of nanoemulsion preparation. Afterward, we aimed to improve the stability of this formulation, and the addition of a hydrophilic surfactant (polysorbate 80) at concentrations of 0.5 to 4% was tested. By means of this study, we observed that the use of 0.5% polysorbate 80 improved the stability of the formulation. This formulation kept its properties throughout the evaluation period (60 days), that is, droplet size about 200 nm, drug content around 95 % and zeta potential around -30 mV. The transmission electron microscopy revealed almost spherical droplets, confirming the results of droplet diameter obtained by photons correlation spectroscopy. The in vitro release study, performed by revearse dialysis method, showed that the release profile of the drug from the nanoemulsions is best described by the higuchi model and is identical to that of a acetonitrile solution of thalidomide. The third and last parte of the work was the characterization of the crystalline precipitates found in the 0.05 % (w/w) thalidomide nanoemulsion by means of the techniques: optical microscopy, differential scanning calorimetry, infrared and X-ray diffraction. The analyzed samples were characterized as the alfa polymorph of thalidomide, differently from the polymorph originally used for nanoemulsions preparation (beta). It could also be observed that formulations prepared with the alfa polymorph lead to the precipitation of alfa crystals, and that the solubility of thalidomide in the oil phase is not affected by the type of polymorph employed
