Alcohol Dose Dumping

What is Alcohol Dose Dumping :

Alcohol Dose Dumping is a phenomenon of drug metabolism in which environmental factors can cause the premature and exaggerated release of a drug.
Reason: Some active substances and/or excipients that exhibit higher solubility in ethanolic solutions compared to water
This can greatly increase the concentration of a drug in the body and thereby produce adverse effects or even drug-induced toxicity.
Dissolution testing Requirement (Study as per FDA guidance):
It should be performed using the optimal apparatus and agitation speed.
Dissolution data should be produced from (n=12) (twelve dosage units) at multiple time points to obtain a complete dissolution profile.
Concentration: 0, 5, 10, 20, and 40 percent alcohol are recommended.
The shape of the dissolution profiles should be compared to determine if the modified release characteristics are maintained, mainly in the first 2 hours.
The f2 values evaluating the similarity (or lack thereof) between the dissolution profiles should be estimated (using 0 percent alcohol as the reference).
The complete report should contain full data (i.e., individual, mean, standard deviation, comparison plots, f2 values, etc.) collected during the evaluation of the in vitro, alcohol-induced, dose-dumping study.

Topic	USFDA	EMA (European Medicines Agency)
Requirement and Methodology	Dissolution Medium: 0.1 N HCl Alcohol Concentration: 0%, 5.0%, 20.0 %, 40.0 % Time Intervals: Every 15 min upto 2 hr	Dissolution Medium: As proposed for routine analysis Alcohol Concentration: 0%, 10.0% and 20.0 % Time Intervals: Not Described
Products to be tested	All opioid Modified Release drug products. More Preferred Modified release product which has the potential effect of alcohol	All Modified Release (MR, SR, DR, etc.)
Acceptance Criteria	Generic Products should show a stable result in dose dumping. Or Generic Product does not release more than the reference product.	If Dose dumping is observed or Suspected- Reformulation. If Alcohol effects can not be avoided- 1. The Same effect should be there are Reference products. 2. Proper justification or demonstration that its lack of clinical relevance shall be provided.

Comparison of USFDA and EMA requirement for Alcohol Dose Dumping