Raman imaging and chemometrics evaluation of natural and synthetic beeswaxes as matrices for nanostructured lipid carriers development

Beeswaxes are interesting solid lipids for the development of nanostructured lipid carriers (NLC), and their origin can be either natural or synthetic. Due to this difference, their performance should be distinct and unstable formulations can be generated. The objective of this work was to investigate miscibility and structural changes (polymorphism) in pre-formulations (blends of solid and liquid lipids) using synthetic and natural beeswaxes in combination with copaiba oil (a natural liquid lipid), in the concentration range of 5.0 to 50.0% (w/w). Raman spectra were acquired over a region of 4 mm2 (mapping mode), dead pixels were removed using Independent Components Analysis (ICA) and Multivariate Curve Resolution Alternating Least Squares (MCR-ALS) was then used to generate the images. Samples were analyzed at the initial time and after 3 months, using the Distributional Homogeneity Index (DHI) and standard deviation of the histograms. The pre-formulation containing synthetic beeswax showed different structural forms before and after melting, and structural changes over time, depending on the amount of the liquid lipid incorporated. These results demonstrate how spectroscopic imaging techniques can be valuable in pharmaceutical development, as well as the importance of choosing the type and proportion of solid lipid to achieve stable NLC formulations.