Influence of emulsifiers on the crystallization of solid lipid nanoparticles.

The crystallization temperature and polymorphism of tripalmitin nanoparticles in colloidal dispersions prepared by melt-homogenization and stabilized with different pharmaceutical surfactants (sodium glycocholate, sodium oleate, tyloxapol, Solutol HS 15, Cremophor EL) and their combinations with soybean phospholipid (Lipoid S100) were investigated to establish the influence of the emulsifiers on these parameters. There were no major effects on the crystallization temperature but remarkable differences in the time-course of polymorphic transitions after crystallization of the triglyceride particles indicate interaction between the surfactant layer and the triglyceride matrix. The metastable alpha-modification was most stable in dispersions solely stabilized with glycocholate. Upon fast cooling from the melt, these dispersions form an uncommon type of alpha-modification that displays only a very weak small-angle reflection indicating poor ordering between triglyceride layers. Slow crystallization of these glycocholate-stabilized nanoparticles yields the usual alpha-form. Electron microscopic investigations reveal that, in both cases, the particles in the alpha-modification are less anisometric than those of the stable beta-form. These results indicate that major rearrangements still may take place in solid lipid nanoparticles after recrystallization.