Absorption of morphine from a slow-release emulsion used to induce morphine dependence in rats

This study was performed to measure absorption of morphine from the injecti on site following treatment of rats with slow-release emulsions formulated with morphine hydrochloride and morphine base. Samples of emulsion were col lected from the injection site of halothane anesthetized animals at 24 and 48 h following emulsion treatment and concentrations of morphine remaining in the emulsion were analyzed using high-performance liquid chromatography (HPLC). In another group of morphine-treated rats, at times equivalent to c ollecting samples of emulsion, the intensity of naloxone-precipitated withd rawal behaviors was monitored. Both morphine base- and hydrochloride-contai ning emulsions induced a high degree of physical dependence in animals trea ted over 48 h. Release of morphine from emulsions containing morphine base was slower than that from the hydrochloride formulations. In the 24-h morph ine base-treated animals, approximately 45% was absorbed from the injection site as opposed to 99% in the 24-h morphine hydrochloride-treated animals. These results suggest that morphine base containing emulsions provide a mo re sustained exposure to the opioid. (C) 1999 Elsevier Science Inc.