Sources of dissolution variability into biorelevant media

Area of Science:

• Pharmaceutical Sciences
• Drug Delivery
• Analytical Chemistry

Background:

• Dissolution testing is critical for drug development and quality control.
• Biorelevant dissolution media offer more physiologically relevant results but can be complex to fabricate and use.
• Variability in dissolution testing can arise from multiple sources, complicating interpretation.

Purpose of the Study:

• To quantify the contributions of various factors to dissolution variability in biorelevant media.
• To identify the most significant sources of variation in dissolution testing.
• To assess the impact of location, operator, media fabrication, day, and tablet on dissolution results.

Main Methods:

• Analysis of Variance (ANOVA) was applied to existing 30-minute dissolution data.
• Data from ibuprofen and ketoconazole dissolution studies were analyzed.
• Factors investigated included location, operator, media fabrication method, day, and tablet.

Main Results:

• Total dissolution variance was highest for medium dissolution rates.
• The rank order of variability sources was location > operator > day > fabrication method > tablet.
• Location was the most impactful source of variability, frequently contributing the majority of the total variance.

Conclusions:

• Location is the primary driver of dissolution variability, consistent with findings using non-biorelevant media.
• Biorelevant media demonstrate favorable repeatability and reproducibility when location effects are considered.
• Controlling for location is crucial for accurate and reproducible drug dissolution testing.