Evaluation of the miscibility and structural modifications of lipids for the development of nanostructured lipid carriers and hydrogels for anesthetic using Raman imaging associated with chemometric methods

Abstract

The use of Nanostructured Lipid Carriers (NLC) in drug delivery has attracted attention in last years. Developed in the end of the 90's, the core of NLC is composed of a mixture of solid lipid and liquid lipids, which allows for high drug upload and increased stability of the nanoparticles. However, the immiscibility between NLC excipients and between excipients and incorporated drugs can generate instability of formulations, often identified only after months. In this sense, Raman spectroscopy imaging can be an important tool in pharmaceutical development because it enables the microscopic evaluation of the distribution of excipients, even at early stages of development. By combining a microscope and a spectrometer, this technique provides chemical and spatial information. However, even then univariate methods are mostly used in this kind of analysis, they are not the always the most indicated, mainly in the case of spectral overlapping, that is very common in this sample. In such cases the use of chemometric methods, mainly multivariate curve resolution, can offer a better resolution. This project aims at developing of a novel methodology for the early selection of lipidic excipients, their proportions and the amount of drug possibly solubilized in both solid and liquid excipients using ternary diagrams and Raman spectroscopy imaging, associating these results with chemical and physical stability of the formulations. For such purpose, several excipients will be evaluated for the solubility of the drugs lidocaine and butamben and the most promising ones will be studied by ternary diagrams. In a second step, NLC formulations containing the selected proportions will be incorporated in hydrogels, which will be also mapped using Raman spectroscopy for characterization and comparison. (AU)