In vitro dissolution of oral modified-release tablets and capsules in ethanolic media.
In 2005, Palladone, an extended-release capsule, was withdrawn from the market after clinical testing showed subjects who took the product with alcohol had increased levels of drug in their blood. To better understand this phenomenon, we studied the in vitro drug release of 27 oral modified-release products in alcohol-containing media. In 40% alcoholic medium, 9 of 10 capsules and 2 of 17 tablets show accelerated drug release. When a high percentage of the total dose is released in a short period of time, the extended-release product is then performing like an immediate release formulation. Products were also tested in 5% and 20% alcoholic media and in simulated gastric fluid (without enzyme) containing 20% alcohol. No tested capsules or tablets exhibited a significant increase in drug release in media containing only 5% alcohol. The current study indicates that in vitro dissolution may provide evidence regarding the ruggedness of formulations to ingested alcohol.
Smith
Anjanette P
AP
U.S. Food and Drug Administration, Division of Pharmaceutical Analysis, St Louis, MO 63101, USA. anjanette.smith@fda.hhs.gov
Moore
Terry W
TW
Westenberger
Benjamin J
BJ
Doub
William H
WH
D000284:Administration, Oral; D002214:Capsules; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000737:chemistry*; D000431:Ethanol / Q000737:chemistry*; D012995:Solubility; D013608:Tablets, Enteric-Coated
D002214:Capsules; D003692:Delayed-Action Preparations; D013608:Tablets, Enteric-Coated; D000431:Ethanol