title: 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.
authors.affiliation: Departments of Anesthesiology, Family Medicine, and Pharmacology, Rush University Medical Center, Chicago, IL 60612, USA. rbarkin@rush.edu
authors.forename: Robert L
authors.initials: RL
authors.lastname: Barkin
authors.forename: Dean
authors.initials: D
authors.lastname: Shirazi
authors.forename: Eric
authors.initials: E
authors.lastname: Kinzler
mesh_terms: D000284:Administration, Oral; D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000737:chemistry*; D002851:Chromatography, High Pressure Liquid; D003692:Delayed-Action Preparations; D000431:Ethanol / Q000737:chemistry*; D009020:Morphine / Q000008:administration & dosage / Q000737:chemistry*; D013607:Tablets; D013997:Time Factors
chemical_list: D000701:Analgesics, Opioid; D003692:Delayed-Action Preparations; D013607:Tablets; D000431:Ethanol; D009020:Morphine