Quality by Design Integration of Design of Experiments for Tablet Formulation Optimization and Process Validation

Area of Science:

• Pharmaceutical Science
• Chemical Engineering
• Drug Development

Background:

• Quality by Design (QbD) and Design of Experiments (DoE) are crucial in pharmaceutical development.
• Current approaches often separate formulation, process optimization, and validation.
• A unified framework is needed for effective tablet development.

Purpose of the Study:

• To provide a comprehensive review of integrating DoE into the full lifecycle of oral tablet development.
• To demonstrate how formulation-level DoE can define, refine, and confirm design space.
• To offer a practical framework for scientists and manufacturing teams.

Main Methods:

• Narrative review of published case studies on oral tablet development.
• Organization of case studies along a formulation-to-validation pathway.
• Focus on translating Target Product Profile (TPP) into quality attributes and using DoE for formulation and process studies.

Main Results:

• DoE outputs support probabilistic and mechanistic design space definition.
• Integration of DoE with scale-up, technology transfer, and process validation (Stages 1-3).
• Challenges identified in integrating DoE with Process Analytical Technology (PAT) and data-driven control.

Conclusions:

• A practical framework for embedding DoE into QbD-based tablet development is presented.
• Key gaps include limited use of probability-based design spaces and digitally enabled validation.
• The review synthesizes DoE applications across the tablet development lifecycle.