Evaluation of olanzapine–excipient compatibility for the development of nanostructured lipid carriers: a preformulation study with lipids and surfactants

Drug-excipient interaction studies are fundamental for the efficient development of new formulations. These interactions directly influence drug stability, loading capacity, controlled release, and bioavailability, which are essential aspects to optimize therapeutic efficacy and minimize possible adverse effects. This research aimed to investigate the physicochemical compatibility of OLZ with lipid excipients intended for NLC formulation. Binary mixtures (1:1, w/w) of OLZ with a range of solid, liquid lipids and surfactants were examined using thermogravimetry (TG/DTG) and differential thermal analysis (DTA), and Fourier-transform infrared spectroscopy (FTIR). Isothermal stress tests were conducted at 60 ± 2 °C for a period of up to 30 days, and the OLZ content was measured using a validated HPLC method. The thermal and spectral analyses indicated interactions between OLZ and excipients such as oleic acid, Capmul®, Captex®, and Span® 60, as demonstrated by shifts or suppression of characteristic OLZ peaks. The degradation observed under stress conditions confirmed limited stability with stearic acid, lauric acid, palmitic acid, glyceryl monostearate, oleic acid, Capmul® and Span®60 and 80 , with OLZ content reduced to 55.6–70.6% after 30 days in the most affected mixtures, compared to 100.0 ± 2.9% for pure OLZ. Overall, these findings emphasize the significance of excipient selection to guarantee stability and compatibility in the formulation of OLZ-loaded NLC systems.