Effect of Ethanol on the Release of Morphine Sulfate From Oramorph SR Tablets

Abstract

Recent data have shown that rapid release of active drug (i.e., dose-dumping) can occur when modified-release formulations of pain medications, and other extended-release pharmacotherapies, are exposed to ethanol in vitro. Dose-dumping of sustained-release opioids is of particular concern because of the risk for serious and potentially fatal adverse events. Sustained-release morphine sulfate tablets (Oramorph SR, 15, 30, 60, and 100 mg; Xanodyne Pharmaceuticals, Inc., Newport, KY) were incubated in vitro at simulated physiologic conditions in media containing no ethanol or ethanol in concentrations ranging from 4%-40% v/v. Morphine sulfate release was measured over the course of 1 to 24 hours using a high-performance liquid chromatography method (United States Pharmacopeia). The sustained-release morphine sulfate tablets exhibited no evidence of active drug dose-dumping. Regardless of ethanol concentration, ethanol exposure did not increase the rate of release of morphine sulfate. Release of approximately 20%-25% of the morphine sulfate dose within 1 hour was consistent among the morphine doses tested and ethanol concentrations. Release of morphine sulfate from the 60- and 100-mg tablets exposed to the higher ethanol concentrations (20% and 40% ethanol) was slightly delayed at all time points beyond 1 hour. The results of this in vitro study suggest that ethanol concentrations as high as 40% do not substantially alter the sustained-release properties of the morphine sulfate tablets.