Correlation between long-term stability of solid lipid nanoparticles (SLN) and crystallinity of the lipid phase.

Aqueous dispersions of solid lipid nanoparticles (SLN) are usually physically stable for more than 3 years. However, in some systems gelation occurred leading to solid gels due to an unknown mechanism. To elucidate this mechanism, Compritol SLN were stored at different temperatures, varying light exposure, in different packing materials and stressed by shear forces in short-term tests and a long-term study of 3 years. The SLN were analyzed by differential scanning calorimetry and sizing techniques. After production by hot homogenization of the melted lipid, the Compritol SLN crystallize in a mixture of stable beta' with unstable polymorphs (alpha, sub alpha). The destabilizing factors light, temperature and shear forces cause a distinct increase in the recrystallization index by transformation of the lipid to the beta' modification being accompanied by gel formation. Physically stable SLN remain as a mixture of modifications, increase in crystallinity index during storage is slow and crystallization occurs mainly in unstable modifications. From this, stabilization of physically critical SLN dispersions seems possible by inhibition of the transformation of the lipid to the stable modification.