Design and characterization of propofol lipid nanocapsules: proof of concept for hospital preparation

Hospital pharmacies are not equipped to produce lipid nanoemulsions, which are generally obtained using high-energy processes. This study reports the development of propofol-loaded lipid nanocapsules using a low-energy spontaneous emulsification process by phase inversion composition. This approach requires minimal equipment and can easily be transposed into continuous production using a microfluidic chip. A formulation containing 2% w/w propofol has been successfully developed. It consists of a mixture of PEGylated surfactants (Kolliphor® HS15, polysorbate 85) and a medium-chain triglyceride (Labrafac® WL1349). Its physicochemical characteristics were compared with those of the marketed product Diprivan 2% using multiangle dynamic light scattering and particle tracking analysis. The nanocapsule dispersion exhibited a narrower size distribution and a much smaller mean diameter (80 nm vs. 250 nm). Stability, evaluated by turbidimetry, was comparable to that of standard marketed nanoemulsions. As with all nanoemulsions prepared by this technique, it contains residual micelles. Tangential flow filtration and asymmetric flow field-flow fractionation demonstrated that these micelles encapsulate little to no propofol, with over 99% of the drug being embedded in the nanodroplets. Due to their small size, the lipid nanocapsules could be sterilized by 0.22 µm filtration. In conclusion, this work as a proof of concept allows us to go forward to developing lipid nanocapsule formulations for tailoring treatments to specific needs populations, for clinical trials, or offers an alternative solution in the event of a shortage of essential lipophilic marketed drugs.