A liposomal dispersion formulation of propofol: formulation, pharmacokinetics, stability, and identification of an oxidative degradant

Propofol is a common and highly effective anesthetic. Commercially available formulations of propofol, which is only sparingly soluble in aqueous systems, utilize emulsion technology. A liposome based dispersion formulation of propofol has been produced which exhibits good long term colloidal and chemical stability and pharmacokinetcs indistinguishable from the emulsion systems. Inclusion of 0.01% ascorbic acid in the final formulation arrests the growth of an oxidative degradant of propofol both during production and on stability. This degradant is identified as being the dimer 4,4′-dihydroxy-3,3′, 5,5′-tetraisopropylbiphenyl by mass spectroscopy and comparison of the infrared spectrum of the purified degradant to predicted spectra generated using density functional theory.