水溶性薬物封入w/o/w type multiple emulsionの調製とその放出性に関する基礎的検討

W/o/w type multiple emulsions containing vancomycin (VCM) in the internal aqueous phases were prepared by a modified two-stage emulsification procedure. We used a lipiodol-soybean oil mixture to minimize the difference in specific gravities between the aqueous phase and the oily phase. Emulsions with high entrapment efficiency (95.54%), good stabilities, small(19.41μm) and homogeneous droplet diameters were obtained by use of 0.5% VCM dissolved in the internal phase, 5% HCO-40 in the oily phase and 5% Pluronic F-88 in the external phase. In a release pattern from the emulsion in vitro, little drug was released for 2 days and then 3.5% of the drug was released in day 3. When 5% solution was entrapped in the internal phase, entrapment efficiency was 86.86%, mean diameter was 14.50 μm, but the formulation showed relatively rapid VCM release in vitro. Moreover from observation of microscopic photographs, each particles were stable in storage and under physiological conditions. Serum concentrations of VCM after administration of the emulsion were sustained. Especially after intraperitoneal administration, the concentrations of VCM released from the emulsion were kept at 1/5 of those after administration of a simple solution. The present findings suggest that the emulsion is stable in vivo and releases VCM gradually.