TRIGLYCERIDE-BASED MICROEMULSION FOR INTRAVENOUS ADMINISTRATION OF SPARINGLY SOLUBLE SUBSTANCES

A pharmaceutically acceptable microemulsion system composed of a mediu m-chain triglyceride (MCT), soybean phosphatidylcholine and poly(ethyl ene glycol)(660)-12-hydroxystearate (12-HSA-EO15) as amphiphiles, and poly(ethylene glycol) 400 (PEG 400) and ethanol as cosolvents is prese nted and characterized in terms of phase behavior, microstructure, sol ubilization capacity and in vivo effects after intravenous administrat ion to conscious rats. At a total concentration of 11.9 wt % of soybea n phosphatidylcholine and 12-HSA-EO15, a microemulsion region was form ed over a wide range of alpha, where alpha is the weight fraction of M CT/(MCT + water + PEG 400 + ethanol). The microstructure of the microe mulsion was of a bicontinuous nature even at high oil concentrations. The mean droplet diameter of the oil-in-water emulsion formed after di lution of microemulsions prepared at different alpha within the one-ph ase region was between 60 and 200 nm. It was concluded that it is poss ible to administer up to 0.5 mL/kg of the microemulsion (alpha = 0.5) without producing any significant effect on acid-base balance, blood g ases, plasma electrolytes, mean arterial blood pressure (MAP), heart r ate (HR), and Pa time (the time between depolarization of atrium and c hamber). At a dose of 1.5 mL/kg, a temporary increase in MAP, a decrea se in HR, and a prolongation of the PQ time were observed.