Injectable nanoemulsions prepared by high pressure homogenization: processing, sterilization, and size evolution

Oil-in-water nanoemulsions are promising colloidal dispersions for the delivery of hydrophobic drugs. The use of polysorbate 80as stabilizing agent in these formulations can improve the delivery of the drug to the brain, thanks to a tropismfor apolipoproteins. The aim of this study was to formulate injectable nanoemulsions stabilized by polysorbate 80, which meet United States Pharmacopoeiaparticle size requirements for parenteral emulsions. Nanoemulsions were prepared by high pressure homogenization and characterized in terms of mean hydrodynamic diameter, Gaussian distribution width, and volume-weighted percentage of fat droplets greater than 1.79 µm (PFAT1.79) or 5 µm (PFAT5). The effect of autoclaving, filtration and loading with nile red(a lipophilic fluorescent dye) on the nanoemulsions was evaluated. Real-time and accelerated stability tests were also performed. To satisfy Unites States Pharmacopoeiaparticle size specifications, nanoemulsions required six homogenization cycles. PFAT5 and PFAT1.79 were the particle size parameters more sensitive to discriminate the effect of homogenization, autoclaving, filtration and loading as well as globule size evolution during real-time stability tests. Results from accelerated stability studies correlated with the PFAT5 values measured over time. Overall, the study demonstrates that all nanoemulsions studied ( autoclaved, filtered or loaded) satisfies United States Pharmacopoeiaparticle size requirements up to 90 days, maintaining PFAT5 to values lower than 0.05% v/v.