Screening for Differences in Early Exposure in the Fasted State with in Vitro Methodologies can be Challenging:...

Area of Science:

• Pharmaceutical Sciences
• Drug Delivery and Formulation
• In Vitro Dissolution and Bioavailability

Background:

• The Biorelevant Gastrointestinal Transfer (BioGIT) system is utilized for early assessment of drug product performance.
• Evaluating dose and formulation impact on drug exposure is crucial for product development.

Purpose of the Study:

• To investigate potential limitations of the BioGIT system.
• To assess the predictive capability of BioGIT for drug exposure under various conditions.

Main Methods:

• BioGIT experiments were conducted using five low solubility, weakly alkaline active pharmaceutical ingredients.
• Formulation and dose variations included tablets, chewable tablets, aqueous solutions, suspensions, and different particle sizes (nano/micronized).

Main Results:

• The ratio of mean BioGIT AUC(0-50 min) values did not predict the ratio of mean plasma AUC(0-60 min) values across all comparisons.
• BioGIT conditions may not accurately simulate gastrointestinal transfer for chewable tablets or aqueous solutions.
• Variability in BioGIT data and non-standard administration (e.g., without water) limit its predictive power.

Conclusions:

• The BioGIT system has limitations in predicting early drug exposure for specific drug products and administration methods.
• Adjustments to BioGIT's gastric pH may be needed for nanocrystal formulations of weak bases.
• Identified limitations may apply to other in vitro assessment systems.