Lipid nanoparticles for brain targeting II. Technological characterization

The aim of this work was to characterize lipid nanoparticles from a rheological point of view, intended for drug delivery after parenteral administration. The conditions to obtain a re-dispersible powder using freeze-drying and spray-drying have also been investigated. Lipid nanoparticles (179.9 ± 6.2 nm) were prepared with the high pressure homogenization technique, using previously established optimal conditions (lipid volume fraction of 0.121), though particle size increased (285.9 ± 4.3 nm) in suspensions produced with higher lipid volume fractions (0.255). Rheology evidenced an expected increase of viscosity with the volume fraction and Newtonian behaviour was observed for volume fractions up to 0.161, while higher volume fractions showed shear thinning and shear thickening. In the suspension with a volume fraction of 0.255, a change of the complex modulus was observed at low shear stress. Freeze-drying and nano spray-drying were suitable only when trehalose was employed as an additive. In the former case, particle size was increased by 18% (198.7 ± 1.1 nm) using 20 fold water dilution. With spray-drying, the use of 20 fold dilution in water:ethanol (8:2) led to particle dimensions of 207.7 ±10.0 (Δsize 20%). In conclusion, cetylpalmitate nanoparticles seem to be suitable for parenteral application, up to volume fractions of 0.16, and pharmaceutical operations, which submit suspensions to shear stress, should not be a critical issue.