The influence of physicochemical properties of preservative compounds on their distribution into various phases of oil in water submicron emulsion.

Phospholipids--stabilized submicron emulsions require the addition of preservatives to destroy or inhibit the growth of microorganisms when these preparations are non-sterile products or when packed in multi-dose containers. This study examined the distribution of four paraben esters--methylparaben, ethylparaben, propylparaben, and butylparaben--that were added into submicron emulsions by de novo emulsification. The distribution of preservative compounds among different phases was determined after separation of submicron emulsions by ultracentrifugation. The compounds with higher lipophilicity were concentrated in the oil phase and phospholipids-rich phase, leading to an increase in oil droplet size. However, the effect of the paraben distribution on zeta potential and pH of emulsion fluctuated depending on the type of phospholipid used. The lower lipophilic compounds were mostly found in the aqueous phase and mesophase. These results signify the possibility that the chemical structures and lipophilicity of preservative compounds affected their distribution in phospholipid-stabilized submicron emulsions. We conclude that the higher concentration of preservatives or their combination may be required for efficient preservation of submicron emulsion products.