各種水溶性薬物封入ｗ／ｏ／ｗ ｅｍｕｌｓｉｏｎの製剤学的性質と体内動態

Abstract

Preparation of water-in-oil-in-water (w/o/w) emulsions containing water-soluble drugs and disposition kinetics of vancomycin after administration of an aqueous solution and w/o/w emulsions were studied. We used drug solution for an internal aqueous phase, oil mixture of Lipiodol Ultra-Fluid® and isopropyl myristate (4.5 : 5.5) containing 5 % HCO-40 for an oily phase and saline containing 5% Pluronic® F-88 for an external aqueous phase with a composition of 1 : 4 : 5. W/o/w emulsions encapsulating water-soluble drugs such as vancomycin hydrochloride, doxorubicin hydrochloride, cytarabine and bovine serum albumin were prepared. Among two methods of preparation, the method using a homogenizer was better for preparation of the w/o/w emulsion. The particle size of the w/o/w emulsion was smaller with an increase in rotation rate of the homogenizer(40.1 μm at 2, 500 rpm and 2.81 μm at 20, 000 rpm). The drug entrapment efficiency was increased with an increase in molecular weight of drugs and decreased with an increase in rotation rate of the homogenizer. When molecular weight and the particle size were smaller, drug release was faster. Serum concentrations of vancomycin released from w/o/w emulsions after i.v injection depended on their particle sizes. The smallest w/o/w emulsion (2.81 μm) showed the highest serum concentration and the concentrations were higher than those after administration of vancomycin solution after 45 min following injection. The emulsion was found in the blood until 120 min after injection. Moreover, when the w/o/w emulsion (41.8 μm) was injected into the portal vein, the emulsion accumulated in the liver. Considering from the serum concentration profile and the existence in the blood, the w/o/w emulsion may be expected to remain in the blood and show sustained drug release.