Solid dispersion of morphine-tristearin with reduced presystemic inactivation in rats

Solid dispersions of morphine in tristearin, beta-sitosterol, and cholesterol were prepared by evaporation of their ethanol solutions. Weight ratios of morphine-lipid of 1:1, 1:3, and 1:4.5 were prepared. Dissolution studies of the solid dispersions and morphine were conducted in a simulated GI medium at 37 degrees. The release rates of morphine from the tristearin dispersions were the slowest. The 1:1 morphine-tristearin dispersion was administered orally to rats. Free and total morphine levels in rat urine were determined by spectrofluorometric and enzymatic immunoassay procedures, respectively. The morphine-tristearin dispersion yielded a higher percentage of free morphine after 24 and 48 hr as compared with morphine and its sulfate.