Towards Virtual Bioequivalence Studies for Oral Dosage Forms Containing Poorly Water-Soluble Drugs: A Physiologically...

Area of Science:

• Pharmacology
• Biopharmaceutics
• Computational modeling

Background:

• Predicting drug bioequivalence for poorly soluble drugs is challenging.
• Physiologically based biopharmaceutics (PBBM) models offer a promising in silico approach.
• Understanding gastrointestinal (GI) physiological variability is crucial for accurate predictions.

Purpose of the Study:

• To develop and validate a PBBM approach for predicting bioequivalence of dosage forms with poorly soluble drugs.
• To assess the impact of human GI physiological variations on bioequivalence predictions.
• To evaluate the accuracy of the PBBM approach using model drugs like aripiprazole and enzalutamide.

Main Methods:

• Utilized in vitro biorelevant dissolution testing and in silico PBBM simulations.
• Incorporated inter-individual variabilities in GI physiological parameters (e.g., gastric emptying, fluid volume).
• Compared different dosage formulations (solution vs. tablet) to assess prediction accuracy.

Main Results:

• The PBBM approach accurately predicted key bioequivalence parameters (geometric mean ratio, 90% confidence interval) for both model drugs.
• Virtual studies demonstrated good prediction of inter-individual performance variations.
• The model successfully differentiated between formulations with varying in vitro dissolution profiles.

Conclusions:

• The developed PBBM approach shows high accuracy in predicting bioequivalence for poorly soluble drugs.
• Further characterization of GI physiological parameters and their variabilities is essential for enhancing prediction precision.
• This in silico method can aid in efficient dosage form development and regulatory assessment.