Drug localization and its effect on the physical stability of poloxamer 188-stabilized colloidal lipid emulsions

Abstract

Colloidal lipid emulsions are a promising formulation option for poorly water-soluble drugs. Due to their complex composition, they provide different sites for the localization of drugs. Drug molecules can be situated in the lipid matrix, in the aqueous phase with its structures formed by an excess of emulsifier or at the droplet interface. The interface and the mechanism of stabilization is mainly characterized by the emulsifier. In this study, the main focus was on the influence of drug localization on the stability of emulsions sterically stabilized with poloxamer188. In addition to 5% of this non-ionic emulsifier, the emulsions contained 10% soybean oil. The localization of the drugs fenofibrate, curcumin, betamethasone valerate, cinnarizine, dibucaine and flufenamic acid within the emulsion system at a physiological pH of 7.4 as well as their influence on emulsion stability were examined. The results indicated that the stability of poloxamer 188-stabilized emulsions can be influenced in a positive or negative way by the localization of drug molecules in the interface of emulsion droplets. Applying cinnarizine as model substance at pH 5, 7.4 and 10, no pronounced change in the localization was detected as a result of alterations in the charge of the drug.