# Recent Advances in Oral Drug Delivery Systems for BCS III Drugs

## TL;DR

This paper reviews strategies to improve oral absorption of BCS Class III drugs, which have high solubility but low intestinal permeability.

## Contribution

The paper provides a mechanism-guided analysis of bioavailability enhancement strategies for BCS III drugs.

## Key findings

- BCS III drug absorption is limited by intestinal permeability, not dissolution.
- No single strategy can universally overcome absorption barriers for BCS III drugs.
- Mechanism-guided strategy selection is essential for effective drug delivery design.

## Abstract

Oral drugs classified under Class III of the Biopharmaceutics Classification System (BCS) are defined by high aqueous solubility yet low intestinal permeability. Their restricted oral bioavailability arises not from inadequate dissolution, but is primarily governed by the intestinal permeability barrier, coupled with substantial inter-individual variability in absorption. This review adopts the intestinal permeability barrier as its core analytical framework to dissect the key determinants of oral absorption for BCS III drugs, while presenting a comparative and critical evaluation of prevailing bioavailability enhancement strategies. From perspectives including mechanism of action, achievable magnitude of enhancement, applicable physicochemical and physiological conditions, and translational feasibility, the intrinsic mechanistic limitations and applicable boundaries of distinct strategies are delineated. Finally, this paper concludes that the absorption barriers of BCS III drugs cannot be universally surmounted by a single strategy, emphasizing the significance of mechanism-guided strategy selection for the rational design of oral drug delivery systems. In doing so, it provides a foundational basis for the rational development of oral delivery systems tailored to BCS III drugs.