The influence of concomitant use of alcoholic beverages on hypromellose matrix tablets - Pharmaceutical Technology

Latest Issue
PharmTech

Latest Issue
PharmTech Europe

The influence of concomitant use of alcoholic beverages on hypromellose matrix tablets


Pharmaceutical Technology Europe
Volume 20, Issue 12

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 systems.

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.


ADVERTISEMENT

blog comments powered by Disqus
LCGC E-mail Newsletters

Subscribe: Click to learn more about the newsletter
| Weekly
| Monthly
|Monthly
| Weekly

Survey
FDASIA was signed into law two years ago. Where has the most progress been made in implementation?
Reducing drug shortages
Breakthrough designations
Protecting the supply chain
Expedited reviews of drug submissions
More stakeholder involvement
Reducing drug shortages
32%
Breakthrough designations
11%
Protecting the supply chain
37%
Expedited reviews of drug submissions
11%
More stakeholder involvement
11%
View Results
Jim Miller Outsourcing Outlook Jim Miller Health Systems Raise the Bar on Reimbursing New Drugs
Cynthia Challener, PhD Ingredients Insider Cynthia ChallenerThe Mainstreaming of Continuous Flow API Synthesis
Jill Wechsler Regulatory Watch Jill Wechsler Industry Seeks Clearer Standards for Track and Trace
Siegfried Schmitt Ask the Expert Siegfried SchmittData Integrity
Sandoz Wins Biosimilar Filing Race
NIH Translational Research Partnership Yields Promising Therapy
Clusters set to benefit from improved funding climate but IP rights are even more critical
Supplier Audit Program Marks Progress
FDA, Drug Companies Struggle with Compassionate Use Requests
Source: Pharmaceutical Technology Europe,
Click here