The effect of ethanol on the release of opioids from oral prolonged-release preparations.
Recent experience has prompted the US FDA to consider whether ethanol ingestion may modify the release characteristics of prolonged-release formulations, where dose dumping may be an issue for patient safety. The influence of ethanol on the in vitro release of opioid drugs from some prolonged-release formulations utilizing different release technologies was examined. Results indicated that the prolonged-release mechanisms remained intact under the testing conditions, although one product showed initial sensitivity to ethanol in its release characteristics. Nevertheless, in this case, extrapolation of the findings to likely outcome in vivo indicated no risk of dose-dumping. It is proposed that prolonged-release medicinal products should be tested during development to ensure robustness to the effects of ethanol on drug release.
Walden
Malcolm
M
Mundipharma Research Limited, Cambridge Science Park, Milton Road, Cambridge, UK. malcolm.walden@mundipharma-rd.eu
Nicholls
Fiona A
FA
Smith
Kevin J
KJ
Tucker
Geoffrey T
GT
D000284:Administration, Oral; D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000737:chemistry*; D003692:Delayed-Action Preparations; D004347:Drug Interactions; D000431:Ethanol / Q000494:pharmacology*; D005746:Gastric Emptying; D006801:Humans; D012995:Solubility
D000701:Analgesics, Opioid; D003692:Delayed-Action Preparations; D000431:Ethanol