Integration of dissolution into physiologically-based pharmacokinetic models III: PK-Sim®

Area of Science:

• Pharmacokinetics and Drug Development
• Computational Biology and Bioinformatics

Background:

• In-silico methods offer cost-effective support for drug development decision-making.
• Physiologically-based pharmacokinetic (PBPK) modeling is a robust computational tool for predicting drug pharmacokinetics.
• PK-Sim is a commercial PBPK software enabling simultaneous simulation of ADME processes across species.

Purpose of the Study:

• To demonstrate the utility of PK-Sim for predicting in-vivo pharmacokinetics.
• To focus on integrating dissolution properties for oral drug administration.
• To evaluate PBPK modeling for diverse dosage form performance.

Main Methods:

• Utilized PK-Sim, a PBPK modeling software.
• Applied mechanistic dissolution modeling (Noyes-Whitney type).
• Conducted three real-life case studies involving PBPK absorption modeling.

Main Results:

• Direct prediction of in-vivo dissolution rates from particle formulation properties.
• Successful prediction of human food effects based on Beagle dog data.
• Demonstrated software utility in developing combined immediate-controlled release formulations.

Conclusions:

• PBPK modeling, particularly with PK-Sim, effectively supports drug development.
• Integration of dissolution data into PBPK models is crucial for oral and non-oral drug administration.
• Future applications include enhanced in-vitro to in-vivo extrapolation for drug formulations.