Sub-50 nm ultra-small organic drug nanosuspension prepared by cavi-precipitation and its brain targeting potential

The purpose of this study was to show whether it is possible to prepare sub 100 nm or preferably sub-50 nm drug nanosuspension (NS) of suitable quality for intravenous administration. Furthermore, we have studied how the brain targeting potential of such small size organic NS differs from relatively bigger size NS. Two combination technologies (cavi-precipitation, H96) and a standard high-pressure homogenization (HPH) technology were used to prepare drug NS of different sizes. The cavi-precipitation process generated the smallest AmB NS, i.e., 27 nm compared to 79 nm by H96 technology and 252 nm by standard HPH technology. Dialysis of the nanosuspension in the original dispersion media was found to be the most efficient solvent removal method without negatively affecting particle size. The removal of organic solvent was found to drastically improve the stability of the formulations. The protein adsorption pattern shows that the small size NS particles obtained by the caviprecipitation process have the potential to circulate longer in the bloodstream and have the potential to be taken up by the blood-brain barrier. The cavi-precipitation process generated ultrafine NS particles, which fulfilled the quality requirements for intravenous administration and offer a potential solution for brain targeting.

Automated summary

This study aimed to prepare drug nanosuspensions of different sizes using various technologies and found that ultrafine particles generated by cavi-precipitation process have potential benefits for intravenous administration and brain targeting. Dialysis was the most efficient solvent removal method and removal of organic solvent drastically improved the stability of the formulations.