(674f) Stabilization of Solid Lipid Nanoparticle Suspensions

Solid Lipid Nanoparticles (SLNs) have great potential as delivery systems for the encapsulation, protection and release of active lipophilic compounds (e.g., drugs, nutraceuticals, antimicrobials, antioxidants and vitamins) in the pharmaceutical, agrochemical, food and personal care industries. SLNs are commonly prepared by making a hot oil-in-water nanoemulsion using high pressure homogenization followed by controlled cooling so that the fluid lipid droplets crystallize and produce solid nanoparticles (r < 100 nm). Compared to other colloidal delivery systems, SLNs offer several advantages for encapsulation of active components including improved physical stability, protection to chemical degradation and precise control over release rates. A major obstacle to the widespread industrial use of SLNs is their tendency to aggregate and form gels when stored at ambient temperatures. A widely accepted theory is that aggregation is driven by the lipid phase undergoing a polymorphic transformation from the thermodynamically unstable α-form to the stable β-form.  An increase in surface area occurs as a spherical α-particle is transformed into a platelet-like or needle-like β-particle, causing a decrease in surfactant coverage on the particle surface. The newly formed surfaces contain lipophilic patches that result in hydrophobic attraction between particles.

Along with several other research groups, we have shown that SLN aggregation can be substantially reduced or even eliminated by mixing specific low-melting point oils with the molten lipid prior to homogenization. While the stabilization mechanism is not well understood, one theory is that the presence of the oil inhibits the large shape change that occurs for pure solidified lipid crystals, thereby reducing hydrophobic attraction between particles. Another theory is that shape change occurs but the oil coats the SLN surface and allows free movement of surfactant at the newly established oil-water interface to stabilize the particles. Currently, the design of stable SLNs must be performed by trial-and-error experimentation to identify a suitable oil, solid lipid and surfactant combination. To facilitate widespread industrial acceptance of SLNs, improved understanding of the stabilization mechanism and the development of systematic methods for designing stable systems are needed.

In this presentation, we report on the effects of different oils on the aggregation stability of certain lipids stabilized with nonionic surfactant in water.   Aggregation dynamics were monitored by measuring particle size distributions with static light scattering. Polymorphic transformation behavior was examined with differential scanning calorimetry. We found that the oil type and concentration strongly affected SLN aggregation behavior.  In the absence of oil, SLNs quickly aggregated and formed a gel. Increasing oil concentrations yielded increasingly stable dispersions while reducing SLN crystallization and melting temperatures. Furthermore, increasing oil concentrations increased the SLN polymorphic transformation rate such that negligible α-particle content was observed at oil concentrations that yielded stable dispersions. Cryogenic TEM images showed that increasing oil concentrations produced more spherical particles. Taken together, these results suggest that oil trapped within the growing SLN crystal matrix accelerates the polymorphic transformation but retards the large shape change normally associated with the transformation.