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 ultratiltration, which procedure allowed to distinguish between the fractions of free preservatives (F-w) and incorporated in the liposomal or micellar region (F-lm). The fractions present in the oily phase and in the interface were calculated. Depending on the formulation, F-w was 17-31% and 2.3-6.0% for paraben M and P, respectively. The F-lm 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. (c) 2006 Elsevier B.V. All rights reserved.