Basic studies on formulation, method of preparation and characterization of water-in-oil-in-water type multiple emulsions containing vancomycin

Abstract

A method of preparing a stable water-in-oil-in-water type multiple emulsion (w/o/w emulsion) as a carrier of peptides was sought by studying rotation rate of homogenizer, mixing ratio of each component and concentrations of surfactants. We used 'Lipiodol Ultra-Fluid® and isoropyl myristate oil mixture (4.5:5.5)' for an oil phase of the w/o/w emulsion to minimize the difference in specific gravity between this phase and an aqueous phase and to reduce the viscosity of the former. w/o/w emulsions entrapping vancomycin hydrochloride in their internal aqueous phases were prepared by a modified two-stage emulsification procedure and their particle size, entrapment efficiency, viscosity, separation and drug release property studied. The particle size of the w/o/w emulsion was smaller with an increase in rotation rate at an emulsification stage (96.3 ± 31.8 μm at 1000 rpm and 2.81 ± 1.37 μm at 20000 rpm), but its entrapment efficiency was slightly reduced with rate increase. The best mixing ratio of internal aqueous phase:oil phase:external aqueous phase was 1:4:5. For surfactants, HCO-40 (5% (w/v)) and Pluronic F-88 (5% (w/v)) were dissolved in the oily and the external aqueous phase, respectively. Drug release from the w/o/w emulsion was extremely slow and sustained, and that property tended to be faster with a decrease in their particle size (0% at 96.3 μm and 2.97 ± 0.41% at 2.81 μm). The stability of w/o/w emulsion of 10 μm diameter was good from observations of optical and scanning electron microphotographs and measurement of w/o/w emulsion diameters. The w/o/w emulsion prepared in this study is viewed as a possible carrier of water-soluble drugs.