Related Experiment Video
Updated: Mar 17, 2026

Validation of Therapeutic Agent Conjugation to Polyvinyl Alcohol-Coated Medical Devices
Published on: November 29, 2024
Exploring the Feasibility of Biowaiver Extension of BCS Class III Drugs with Site-Specific Absorption Using
Le Sun1, Jin Sun2, Zhonggui He3
1Department of Pharmaceutics, School of Pharmacy, China Medical University, No. 77 Puhe Road, Shenyang North New Area, Shenyang, 110122, China.
Background And Objectives:
The US Food and Drug Administration, World Health Organization and European Medicines Agency have allowed biowaiver for some BCS class III drugs, but shortened the requisite dissolution time of BCS class III drugs from 30 to 15 min, considering their site-specific absorption and others risk. The objective of this study was to assess the effects of site-specific absorption, low absorbed fraction (F a) and gastric emptying rate on the biowaiver extension of BCS class III drugs.
Methods:
The oral absorption of BCS class III drugs nadolol, acebutolol and atenolol which were P-gp substrates, was simulated using GastroPlus software with physiological parameters reflecting site-specific and site-independent absorption. Then, the simulation results were compared with the experimental data in literature. Simulation with different dissolution rates (>85 % solubility, T 85 % = 15-180 min) was performed to predict absorption (maximum concentration, C max and area under the concentration-time curve from time 0 to infinity, AUC0-inf) of the above model/virtual drugs (F a 3.81-80.14 %).
Results:
The results of this study indicated that the site-specific absorption and low F a magnified the effect of dissolution rate on C max and AUC0-inf. However, the oral absorption of model drugs was not sensitive to the change of gastric emptying rate from 0.1, 0.25, 0.5 to 1 h.
Conclusions:
Based on the results of this study, we suggest that for BCS class III drug with high F a (about >80 %), the biowaiver should extend to rapid dissolution (T 85 % = 30 min), and 30 % of F a as the boundary of intermediate permeability class (30 % < F a < 85 %).
More Related Videos
Related Concept Videos
Bioequivalence studies: Biowaivers
Methods for Studying Drug Absorption: In vitro
The diffusion cell method uses a two-compartment cell, including a donor compartment with the drug solution, which simulates the environment where the drug is applied, and a receptor compartment with a buffer solution, which simulates the environment...
Bioavailability Enhancement: Drug Stability Enhancement and GI Retention
Bioavailability Enhancement: Determination and Conceptual Approaches in Overcoming Bioavailability Problems
Methods for Studying Drug Absorption: In situ
The Doluisio method involves perfusing a prepared segment of a rat's small intestine with a solution of radiolabeled drug and a non-absorbable marker. This helps to differentiate between absorbed and non-absorbed drug concentrations. The intestinal segment is connected at both ends using tubing and syringes,...
Bioavailability Enhancement: Drug Permeability Enhancement

