Characterization of diazepam submicron emulsion interface: role of oleic acid

Oleic acid markedly improved the physical stability of a diazepam submicron emulsion. The zeta potential of the emulsion increased with increased oleic acid concentration. This effect suggested that adjustment of the diazepam submicron emulsion pH to 7.8-8.0 led to the ionization of oleic acid molecules at the oil/water (o/w) interface without being excluded from the surface regions of the oil droplets. TEM freeze-fracturing examination revealed that a mixed-emulsifier monolayer film was established at the o/w interface of the submicron emulsion. No liquid crystal or liposome formation was detected. This was confirmed by the results of phosphatidylethanolamine surface labelling at the o/w interface of the emulsion. The improved stability properties conferred to the emulsion by oleic acid should be attributed not only to the zeta potential increase, but also to the strengthening of the molecular interactions occurring between phospholipid and poloxamer emulsifiers in the presence of an ionized form of oleic acid at the o/w interface of the emulsified oily droplets as evidenced in independent monolayer studies.