Physical properties and stability of two emulsion formulations of propofol

We have compared the physical properties of two commercial emulsion formula tions of the intravenous anaesthetic propofol. (Diprivan(R). AstraZeneca. a nd Propofol Intravenous Emulsion, Gensia Sicor Pharmaceuticals) which appea r to differ primarily in the additive content and formulation pH. Diprivan( R) contains disodium edetate and has a pH of 7-8.5, while the Gensia produc t contains sodium metabisulphite and is formulated to a pH of 4.5-6.4. The average zeta potential of Diprivan(R) at pH 8 was -50 mV while that of the Gensia product at pH 4-5 was -40 mV. This information suggests that the phy sical stability of Propofol Intravenous Emulsion should be lower than that of Diprivan(R). Three random batches of both products were subjected to a r ange of stability tests, including shaking, thermal cycling, and freeze tha w cycling, and the emulsion droplet size distribution was then assessed by dynamic light scattering, light diffraction, and electrical and optical zon e sensing. Both emulsions initially showed narrow submicrometre particle si ze distributions. An increased level of droplets larger than 5 mum could be detected in Propofol Intravenous Emulsion after as little as 4 h shaking ( 300 strokes/min at room temperature) and visible free oil could be detected after 8-12 h shaking. In contrast, Diprivan(R) showed no increase in the l arge droplet count after shaking for times up to 16 h. A similar difference in the emulsions was found after one freeze-thaw cycle, with Propofol Intr avenous Emulsion exhibiting extensive coalescence, while that of Diprivan(R ) was at the limits of detection. We conclude that these two products have different physical stability characteristics, and that this may in part be due to the reduced zeta potential in Propofol Intravenous Emulsion compared to that of Diprivan(R). (C) 2001 Published by Elsevier Science B.V.