Thermal analysis of the crystallization and melting behavior of lipid matrices and lipid nanoparticles containing high amounts of lecithin

Abstract

Lipid nanoparticles (LNP) based on triglycerides containing high amounts of the amphiphilic lipid lecithin have been proposed as a promising alternative drug delivery system with regard to drug loading capacity. Aim of the present study is to evaluate the influence of lecithin within the lipid matrix (LM) on the crystallization behavior by thermoanalysis and wide angle X-ray diffraction (WAXD). The crystallinity of LM and LNP is mainly determined by the triglyceride content. However, lecithin influences the crystallization behavior significantly. WAXD shows an accelerated polymorphic transition of the LM to the β-modification upon storage with increasing lecithin content. Both, the melting point and the crystallization temperature are not affected by the lecithin concentration and are comparable to recrystallized triglyceride bulk. However, the crystallinity indices (CI) of LM show a general decrease by 10% suggesting an incomplete crystallization. For the formation of LNP at least 10% lecithin is necessary and all systems are present in the stable β-modification. In comparison to the undispersed LM, the crystallization temperature of LNP is significantly decreased by about 20 °C whereas the melting point is reduced by about 5 °C only. Melting enthalpy is comparable to the untreated triglyceride bulk and elevated in comparison to the undispersed LM. Isothermal heat-conduction microcalorimetry (IMC) enables the determination of crystallization kinetics after fitting of the heat flow volume according to the Avrami equation.