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

    loading  Checking for direct PDF access through Ovid


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.

Related Topics

    loading  Loading Related Articles