Partitioning of parabens between phases of submicron emulsions stabilized with egg lecithin

Partitioning of methyl and propyl parabens (methyl and propyl hydroxybenzoate, paraben M and P) between the major phases in the parenteral submicron emulsions was studied. The investigated emulsions contained 10% or 20% soya-bean oil, 1.2% or 2.4% egg lecithin, 0.18% or 0.36% paraben M and 0.02% or 0.04% paraben P. The aqueous phase was obtained by ultracentrifugation, and subsequently, it was subjected to ultrafiltration, which procedure allowed to distinguish between the fractions of free preservatives (Fw) and incorporated in the liposomal or micellar region (Flm). The fractions present in the oily phase and in the interface were calculated. Depending on the formulation, Fw was 17-31% and 2.3-6.0% for paraben M and P, respectively. The Flm values were in a very narrow range, i.e. 3.0-6.0% for both preservatives. Substantial accumulation, i.e. 38-58% was found in the interface and the partitioning into this region was related to the oil/lecithin ratio rather than to lipophilicity of the preservative.