Using the refined Developability Classification System (rDCS) to guide the design of oral formulations.

Area of Science:

• Pharmaceutical Sciences
• Drug Development
• Biopharmaceutics

Background:

• Assessing biopharmaceutical risks is crucial for oral drug formulation development.
• Existing systems like the Biopharmaceutics Classification System (BCS) offer a foundational classification but can lack nuance.
• There is a need for comprehensive, animal-free approaches to guide formulation design.

Purpose of the Study:

• To demonstrate the practical application of the refined Developability Classification System (rDCS) framework.
• To guide oral formulation design for diverse active pharmaceutical ingredients (APIs).
• To compare rDCS classifications with BCS classifications and evaluate rDCS reliability.

Main Methods:

• Application of the advanced rDCS framework to six diverse APIs.
• Classification of APIs using both rDCS and BCS.
• Comparison of rDCS and BCS classifications.
• Validation of rDCS predictions against literature data on development and pharmacokinetics.

Main Results:

• The rDCS provides a more nuanced risk assessment compared to BCS for several APIs.
• Acetaminophen, voriconazole, and lemborexant were classified favorably by both systems.
• Fedratinib showed stratified risk in rDCS, dependent on in vivo supersaturation.
• Voxelotor and istradefylline were classified in rDCS class IIb, indicating a need for solubility enhancement.

Conclusions:

• The rDCS reliably supports oral formulation design across a wide range of API characteristics.
• The rDCS offers a comprehensive, animal-free approach to biopharmaceutical risk assessment.
• This framework provides a strong foundation for guiding the development of oral drug formulations.