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 injection site following treatment of rats with slow-release emulsions formulated with morphine hydrochloride and morphine base. Samples of emulsion were collected 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 collecting samples of emulsion, the intensity of naloxone-precipitated withdrawal behaviors was monitored. Both morphine base- and hydrochloride-containing emulsions induced a high degree of physical dependence in animals treated over 48 h. Release of morphine from emulsions containing morphine base was slower than that from the hydrochloride formulations. In the 24-h morphine 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 more sustained exposure to the opioid.