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.
Comparison of USFDA and EMA requirement for Alcohol Dose Dumping:
| 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. |
More to Read:
- Acronyms and Abbreviation
- Alcohol Dose Dumping-FDA EU Guideline
- GLP
- Gas Chromatography Columns
- Why is 70% the More Effective Concentration of Isopropyl Alcohol for Disinfection?
- Difference between Incidence and Deviation
- Differential Scanning Calorimetry (DSC)
- Paper Chromatography
- Thin Layer Chromatography
- Difference Between Thin Layer and Paper Chromatography
- Type of Glass container used in Pharmaceuticals
- Fume Hood
- Type of HPLC Column
- Type of Capsules
- Advantages and Disadvantages of Capsules
- Gelatin
- Type of HPLC Detectors
- Alcohol induced dose dumping
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