비페닐디메칠디카르복실레이트 주사제의 설계 및 평가

Design and Evaluation of Biphenyl Dimethyl Dicarboxylate Injections

In an attempt to develop an injectable form of practically insoluble biphenyl dimethyl dicarboxylate (DDB), the effect of various vehicles, cosolvents and hydrotropic agents was investigated. It was found that polyethylene glycol (PEG) 400 revealed the best solvency toward DDB (17.7mg/ml at 370C), and decreasing order of the solubility was as follows: PEG 400 > PEG 300 > diethylene glycol monoethyl ether (DGME) > PEG-8 glyceryl caprylate/caprate. Among the hydrotropes used, sodium salicylate, sodium benzoate and nicotinamide were effective in increasing the solubility in water. The solubility of DDB in 2M sodium salicylate, sodium benzoate and cotinamide solutions was increased 44.3, 23.5 and 44.0 times than that in water, respectively. The addition of sodium salicylate and sodium benzoate to PEG 300-water, PEG 400-water and DGME-water cosolvents remarkably increased the solubility of DDB, and significantly retarded precipitate formation when mixed with water. Hemolytic properties of DDB injections (2mg/4~10ml) in PEG 300-water or DGME-water (60:40 v/v) cosolvents containing sodium benzoate (0.14~0.35M) were very low. It was concluded from the results that these solutions would be applied to the design of new DDB injections.