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.
The size-dependent behavior of different crystalline, colloidal monoacid and complex triglycerides in aqueous dispersion is investigated, mainly by differential scanning calorimetry and X-ray diffraction. With decreasing particle size the melting range of the triglycerides broadens and shifts to lower temperatures. The melting of particles in small-size dispersions (e.g., with mean particle sizes around 100 nm) of even, saturated monoacid triglycerides such as tripalmitin and trimyristin is characterized by a sequence of discrete sharp transitions which are not due to polymorphism. This complex melting process is observed with different types of stabilizers. The sequence of melting events originates from the shape and layered structure of the triglyceride nanocrystals leading to successive discrete transitions corresponding to the melting of particle fractions with different thickness. In dispersions of complex triglycerides, the individual transitions are less sharp or even undetectable. The heat of fusion and the crystallization temperature of the nanoparticles decrease slightly with decreasing particle size whereas the rate of polymorphic transitions increases. Moreover, dispersions containing extremely small nanoparticles display an X-ray diffraction pattern indicating the presence of a crystal form that seems not to have been described previously for these triglycerides.
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