Multimedia Dissolution Testing (MMD) testing refers to evaluating the dissolution profile of a drug product in various media representing different physiological and biorelevant conditions. This approach is essential to meet the requirements of global regulatory bodies, as it helps ensure the drug's consistent performance in diverse conditions.
1. USFDA
General Requirements:
Perform dissolution testing in at least three media of varying pH:
Acidic (pH 1.2).
Neutral (pH 4.5).
Alkaline (pH 6.8).
For poorly soluble drugs, media with surfactants may be required.
Biorelevant Media:
For BCS Class II and IV drugs, use surfactant-based media like SDS or Tween 80.
Biorelevant media like FaSSIF (Fasted State Simulated Intestinal Fluid) and FeSSIF (Fed State Simulated Intestinal Fluid) are encouraged for in-vivo correlation.
Purpose:
To establish discriminatory power and assess the impact of pH on drug release.
2. EMA
General Requirements:
Use media that reflect physiological conditions (pH 1.2, 4.5, 6.8).
For modified-release formulations, additional testing at intermediate pH levels may be required.
Emphasis:
Establishing in-vitro/in-vivo correlation (IVIVC) is highly emphasized.
Biorelevant dissolution testing is often mandatory for biowaivers.
Special Considerations:
Evaluate performance under stressed conditions (e.g., varying ionic strengths).
Testing in FaSSIF and FeSSIF is often recommended for high-fat meal impact assessment.
3. WHO
General Requirements:
Testing in pH 1.2, 4.5, and 6.8 media.
Use of sink conditions for poorly soluble drugs.
Biowaivers:
Accept multimedia dissolution profiles for BCS Class I and III drugs to justify waivers.
Special Notes:
Regional adaptations may apply for countries following WHO guidance.
4. ICH
General Approach:
Encourages harmonization across regions (US, EU, Japan).
pH 1.2, 4.5, and 6.8 are the standard for multimedia testing.
Key Focus:
Aligns with Q6A to ensure reproducibility and relevance.
5. TGA
General Requirements:
Similar to EMA and USFDA, requires testing in pH 1.2, 4.5, and 6.8.
For controlled-release products, additional testing at physiological transit times may be required.
Emphasis:
Testing under biorelevant and stressed conditions to reflect local patient populations.
6. MHRA
General Requirements:
Testing in three key media (pH 1.2, 4.5, 6.8).
Special Focus:
Specific guidelines for orally disintegrating tablets and modified-release formulations.
General Observations Across Regulatory Bodies:
1. BCS Class I and III Drugs:
Often allowed biowaivers if consistent multimedia profiles are demonstrated.
2. BCS Class II Drugs:
Requires rigorous testing in surfactant-based media for in-vitro/in-vivo correlation.
3. Modified Release Products:
Testing across extended pH ranges and at different transit times.
- Good Dissolution Practice
- Comparative Dissolution Profile Guideline
- Dissolution Method Development and Validation
