The Biopharmaceutics Classification System: subclasses for in vivo predictive dissolution (IPD) methodology and IVIVC

Area of Science:

• Pharmaceutical Sciences
• Drug Development
• Regulatory Science

Background:

• The Biopharmaceutics Classification System (BCS) is widely used in drug discovery and development, classifying drugs based on solubility and permeability.
• Its mechanistic basis has led to broad acceptance for drug product development and regulation.
• However, complexities in in vitro and in vivo drug behavior necessitate further refinement.

Purpose of the Study:

• To propose a sub-classification extension of the BCS for Classes II and IV drugs.
• To incorporate acid (a), base (b), and neutral (c) specifications based on pKa.
• To enhance the development of in vivo predictive dissolution (IPD) methodologies.

Main Methods:

• Proposed a sub-classification of BCS Classes II and IV based on drug pKa (acid, base, neutral).
• Considered the impact of pKa on solubility and dissolution in vitro and in vivo.
• Evaluated the influence of gastrointestinal tract variability on dissolution prediction.

Main Results:

• The proposed sub-classification refines the understanding of drug behavior for BCS Class II and IV drugs.
• This approach is crucial for developing in vivo predictive dissolution methodologies.
• It facilitates the assessment of formulation performance and the establishment of dissolution standards.

Conclusions:

• Extending the BCS with acid-base-neutral sub-specifications offers a more mechanistic approach to drug product development.
• This refinement is vital for creating robust in vivo predictive dissolution methods.
• The enhanced BCS classification supports Quality by Design (QbD) and in vitro-in vivo correlations (IVIVC).