Dissolution Requirements of IGDRP Participants
The International Generic Drug Regulators Programme (IGDRP) brings together regulatory authorities from different countries and regions to harmonize and standardize practices for generic drug evaluation. Dissolution testing is a critical part of this process, ensuring the quality and bioequivalence of generic formulations across global markets. Below are the key dissolution requirements typically considered by IGDRP participants:
IGDPR Participating Countries/Regions
- Australia
- Brazil
- Canada
- Colombia
- European Union (EU)
- New Zealand
- Singapore
- South Africa
- South Korea
- Switzerland
- Taiwan
- USA
- WHO (World Health Organization)
Key Dissolution Requirements
pH Conditions:
Dissolution is tested across a range of pH values to simulate different parts of the gastrointestinal tract:
- pH 1.2 (stomach acidity)
- pH 4.5 (intestinal environment)
- pH 6.8 (near-neutral environment)
Some agencies require broader ranges, such as pH 1 to 7.5 or pH 1.2 to 6.8, ensuring solubility in all physiological conditions.
Volume of Dissolution Media:
- Testing generally uses 900 mL or less of dissolution media to maintain sink conditions.
Surfactants:
- Surfactants (e.g., SLS) may be accepted in the media to enhance solubility for poorly soluble drugs, depending on the agency.
Enzymes for Gelatin Coating:
- For capsules or tablets with gelatin coatings, enzymes are added to simulate digestion and ensure accurate dissolution results.
Similarity Factor (f₂):
- A statistical measure used to compare the dissolution profiles of test and reference formulations.
- Typically, f₂ ≥ 50 indicates similarity.
Alternative Models to f₂:
- Some regulatory bodies allow alternative methods for evaluating dissolution profiles.
Sampling Time Points:
- Dissolution is tested at defined time intervals, such as 5, 10, 15, 20, 30, 45, and 60 minutes.
Temperature:
- Testing is conducted at 37 ± 0.5°C or 37 ± 1°C, simulating human body temperature.
Apparatus and Conditions:
Common apparatus include:
- Paddle: Rotations of 50 or 75 rpm.
- Basket: Rotations of 100 rpm.
Different settings are applied based on the formulation type.
Special Conditions:
- Fasted and fed state testing to assess drug dissolution under varying physiological conditions.
- Use of Quality Control (QC) media for routine testing.
Regulatory Variations:
Each IGDRP participant (e.g., FDA, EMA, TGA) may have specific dissolution requirements. Key differences include:
- pH ranges to be tested.
- Acceptance of surfactants or enzymes.
- Sampling points for dissolution data.
- Statistical methods for profile comparison.
By aligning these dissolution requirements, the IGDRP aims to streamline generic drug approvals and ensure consistent quality and therapeutic equivalence worldwide.
Read also:
- Comparative Dissolution Profile Guideline
- Understanding the Q Value in Dissolution Testing
- Factors Affecting Dissolution of Pharmaceutical Products
Resource Person: Moinuddin syed. Ph.D, PMP®