Can your drug product handle alcohol?
For MR drug products, this isn’t a provocative question, it’s a formulation and a regulatory one
Because if alcohol disrupts the release-controlling mechanism of an MR product, the result may be alcohol-induced dose dumping – rapid, unintended drug release from a product that was supposed to release slowly over time.
And that is not a just a dissolution profile shift, that is a potential safety risk.
Which means this study should never be reduced to: “Just run a dissolution study with ethanol.”
It is whether alcohol has compromised the release-controlling mechanism of the product.
Both FDA and EMA try to answer the same question.
What changes is how that question is answered.
For the FDA, the comparison is against the product’s own profile without ethanol (0% ethanol) using the non-alcohol condition as the direct reference point.
Why?
Because the question is: Does alcohol alter the release behavior of this formulation compared with its normal intended performance?
So, the 0% ethanol profile becomes the reference point.
For the EMA, the comparison is framed differently.
EMA arrives at the same non-alcohol anchor- through compliance with dissolution specifications in the QC medium. Essentially whether alcohol changes the product’s behaviour compared with its normal intended performance.
Additionally for generics, through comparison of test and reference products in media with and without alcohol.
So, while the study design and acceptance criteria frame differs, both FDA and EMA are anchored to performance without alcohol, but one does it through direct profile comparison and the other through specification compliance plus comparative test vs reference assessment.
Read also: How do We Ensure that Split Tablets Maintain Dose Accuracy and Stability?
Resource Person: Pearl Pereira Nambiar