Developing In Vitro-In Vivo Correlation for Bicalutamide Immediate-Release Dosage Forms with the Biphasic In Vitro...

Area of Science:

• Pharmacokinetics
• Drug Delivery Systems
• Biopharmaceutics

Background:

• The biphasic dissolution system models the interplay between drug dissolution and absorption.
• It is a promising approach for predicting in vivo drug absorption.
• Bicalutamide (BIC), a BCS Class II drug, exhibits pH-independent poor solubility and high permeability.

Purpose of the Study:

• To evaluate the suitability of biphasic in vitro dissolution testing for establishing an in vitro-in vivo correlation (IVIVC).
• To assess the IVIVC for both original and generic immediate-release (IR) bicalutamide (BIC) tablets.
• To determine the predictive capability of the biphasic system for generic drug development.

Main Methods:

• Dissolution testing was performed using USP apparatus II (paddle method).
• A Level A IVIVC was established by correlating in vitro partitioning data with in vivo absorption data.
• Pharmacokinetic (PK) analysis was conducted using single-compartmental modeling to estimate generic product plasma concentrations.

Main Results:

• A robust correlation (r² = 0.98) was observed between in vitro and in vivo data.
• The ratios of area under the concentration-time curve (AUC) and maximum plasma concentration (Cmax) for generic to original bicalutamide were 1.04 ± 0.01 and 0.951 ± 0.026, respectively.
• These results indicate bioequivalence between the generic and original formulations.

Conclusions:

• Biphasic dissolution testing serves as a valuable in vivo predictive tool.
• This method is particularly useful for developing generic products of poorly soluble, highly permeable drugs like bicalutamide.
• The study validates the biphasic system's utility in ensuring generic drug quality and performance.