Conventional vs Mechanistic IVIVC: A Comparative Study in Establishing Dissolution Safe Space for Extended Release...

Area of Science:

• Pharmaceutical Sciences
• Biopharmaceutics
• Drug Delivery

Background:

• In vitro-in vivo correlation (IVIVC) is crucial for extended-release oral dosage forms, aiding in regulatory submissions and process changes.
• Conventional IVIVC is widely used, but mechanistic IVIVC, incorporating physiological aspects, presents an attractive alternative.
• USFDA guidance has supported the use of IVIVC for over two decades for various regulatory applications.

Purpose of the Study:

• To comparatively evaluate mechanistic and conventional IVIVC for establishing dissolution safe space.
• To assess the flexibility and potential of mechanistic IVIVC in drug development.
• To utilize divalproex sodium and tofacitinib extended-release formulations as case studies.

Main Methods:

• Conventional IVIVC was established using Phoenix software.
• Mechanistic IVIVC was developed using the Gastroplus physiologically based biopharmaceutics model (PBBM).
• Virtual dissolution profiles were generated using the Weibull function and validated internally and externally.

Main Results:

• Mechanistic IVIVC resulted in a wider dissolution safe space compared to conventional IVIVC.
• The study successfully established safe space using both absolute error and T/R ratio methods.
• Virtual dissolution profiles were integrated into both IVIVC models for analysis.

Conclusions:

• Mechanistic IVIVC provides a more flexible approach by integrating physiological aspects.
• Mechanistic IVIVC demonstrates greater potential for establishing a wider dissolution safe space.
• The findings suggest mechanistic IVIVC can enhance the ability to avoid clinical studies for extended-release formulations.