Pharmaceutical products and alcohol
Labels warning against the concomitant use of alcohol and products that contain alcohol-interactive (AI) drugs are used where
appropriate. For other actives (non-AI) that do not have a pharmacokinetic or pharmacodynamic interaction with alcohol, a
warning on the adverse consequence of alcohol consumption caused by the potential for dose dumping may not be present on a
product label.30 The study conducted by Pringle et al. found that 19% of AI and 26% of non-AI drug users reported concomitant alcohol consumption.31
In 2005, FDA issued an alert to healthcare professionals regarding an alcohol-Palladone (Purdue Pharma, CT, USA) interaction.32 This alert cited an increase in the peak plasma concentration of the drug, hydromorphone, to potentially lethal levels because
of the breakdown of the dosage form when ingested with significant amounts of alcohol (240 mL of 4, 20 or 40% ethanol). A
pharmacokinetic study of healthy volunteers showed that co-ingestion of a Palladone capsule with 240 mL of 40% alcohol caused
an average peak drug concentration that was approximately six times greater than when taken with water. One subject also experienced
a 16-fold increase when the capsule was ingested with 40% alcohol compared with water. In a few volunteers, 240 mL of 4% alcohol
(equivalent to two thirds of a typical serving of beer) resulted in almost twice the peak drug plasma concentration compared
with when the capsule was ingested with water.
Shortly after the FDA alert, Meyer and Hussain reported an overall lack of attention in pharmaceutical science literature
and the regulatory assessment process regarding consumption of alcoholic beverages with certain dosage forms, including ER
tablets and capsules.30 FDA has subsequently issued advice to minimize the risk of alcohol-induced dose dumping. Therefore, potential effects on
the release characteristics of an active substance by alcohol have to be thoroughly evaluated for currently marketed products
and new drug applications that utilize an ER mechanism.
Hydro-alcoholic media and the performance of ER formulations
Since the FDA alert, there have been a number of reports on the influence of hydro-alcoholic media on the performance of ER
Koziara et al. claimed increased permeability, elasticity and swelling of cellulose acetate (CA): polyethylene glycol (99:1 w/w) semipermeable
membranes used for osmotic ER drug delivery in 0–60% ethanol solutions.33 Although a slight increase in drug release from the OROS (ALZA Corp., CA, USA) ER systems was recorded, the CA membrane
maintained its functionality and no dose dumping was observed.
Fadda et al. studied the influence of hydro-ethanolic media on the release of mesalamine from Pentasa (Ferring, Switzerland) tablets comprising
ethylcellulose coated granules.34 The time required for releasing 50% of the drug (T50%) was 120 min and 170 min in the absence and presence of ethanol, respectively. This was explained by the lower solubility
of mesalamine in the presence of ethanol.
Roberts et al. studied the influence of hydro-ethanolic media on the dissolution rate of aspirin from HPMC (METHOCEL K4M; Dow Chemical Co.,
MI, USA) matrix tablets.35 They found that aspirin release increased with increasing alcohol concentration in the dissolution media, correlating with
the drug's solubility, but did not result in dose dumping. In 40% ethanol, an initial rapid aspirin dissolution rate was reported
that was explained by a slower initial interaction between alcohol and HPMC. Using cloud point study results, the authors
indicated that ethanol retarded the hydration of the polymer.