Medium scale production of solid lipid nanoparticles (SLN) by high pressure homogenization.

Solid lipid nanoparticles (SLN) were produced by high pressure homogenization using piston-gap homogenizers. Batch sizes varied between 40 ml and 50 l. Because of the different batch sizes, different homogenizer types were used, but the same functional principles were maintained, and the change from 40 ml to 50 l was not critical. With increasing batch sizes, the product quality in terms of particle size distribution and physical storage stability improved. Medium scale (30 l and 50 l) drug-free and drug-loaded SLN batches could be produced reproducibly and batch-to-batch uniformity was proven: within one batch particle sizes were homogeneous. This study revealed the influence of pressure and temperature for the hot homogenization technique A change of pressure between 300-500 bars induced only minor differences in particle size, but some influence of the heating temperature was found. More important than control of the heating process was the control of the cooling process of the final product. A too rapid cooling deteriorated the product quality: cooling with water of 18 degrees C proved to be the optimum cooling condition.