Linking formulation composition to pharmacokinetic and pharmacodynamic responses: a predictive framework for sustained-release tablets
4 affiliations
- 1School of Pharmacy, Sungkyunkwan University, Suwon, Gyeonggi, Korea
- 2College of Pharmacy, Daegu Catholic University, Gyeongsan, Gyeongbuk, Korea
- 3College of Pharmacy, Chung-Ang University, Seoul, Korea
- 4Department of Global Innovative Drugs, The Graduate School of Chung-Ang University, Seoul, Korea
Abstract
The development of sustained-release formulations remains largely empirical and often requires iterative in vitro and in vivo studies to achieve desired pharmacokinetic profiles and therapeutic outcomes. In this study, we developed a formulation-driven predictive framework that links formulation composition to pharmacokinetic and pharmacodynamic responses by integrating design of experiments (DoE), in vitro–in vivo correlation (IVIVC), and population pharmacokinetic/pharmacodynamic (PK/PD) modeling. This approach enables the prediction of both plasma concentration–time and pharmacodynamic response–time profiles directly from formulation composition. Using ticagrelor as a model drug, nineteen sustained-release formulations were prepared and characterized in vitro based on a mixture design with three formulation variables. Three formulations spanning fast, medium, and slow dissolution rates were selected for in vivo pharmacokinetic and pharmacodynamic evaluation in beagle dogs. In vitro dissolution kinetics were described using a Michaelis–Menten model, and the maximum dissolution rate (Vmax) was used as a common linking parameter across the DoE, IVIVC, and PK/PD components. A population PK/PD model incorporating time-dependent dissolution and site-dependent absorption processes was established, and a Level A IVIVC was developed by correlating in vitro and in vivo Vmax values. The framework was validated using both internal and external formulations and successfully predicted pharmacokinetic and pharmacodynamic profiles from formulation composition alone. Prediction errors were within 12.70% for internal validation formulations and within 9.67% for an additionally prepared external validation formulation, meeting FDA criteria for IVIVC predictability. This framework provides a mechanistically grounded strategy for model-informed optimization of sustained-release tablet delivery systems.
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BibTeX
@article{song2026linking,
title = {{Linking formulation composition to pharmacokinetic and pharmacodynamic responses: a predictive framework for sustained-release tablets}},
author = {Sungmin Song and Meoung Jun Park and Jun Hyung Pyo and Tae Hwan Kim and Beom Soo Shin and Soyoung Shin},
journal = {Drug Delivery},
year = {2026},
month = oct,
doi = {10.1080/10717544.2026.2752652},
url = {https://doi.org/10.1080/10717544.2026.2752652},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Linking formulation composition to pharmacokinetic and pharmacodynamic responses: a predictive framework for sustained-release tablets
AU - Sungmin Song
AU - Meoung Jun Park
AU - Jun Hyung Pyo
AU - Tae Hwan Kim
AU - Beom Soo Shin
AU - Soyoung Shin
PY - 2026
DA - 2026/10/27
JO - Drug Delivery
DO - 10.1080/10717544.2026.2752652
UR - https://doi.org/10.1080/10717544.2026.2752652
AB - The development of sustained-release formulations remains largely empirical and often requires iterative in vitro and in vivo studies to achieve desired pharmacokinetic profiles and therapeutic outcomes. In this study, we developed a formulation-driven predictive framework that links formulation composition to pharmacokinetic and pharmacodynamic responses by integrating design of experiments (DoE), in vitro–in vivo correlation (IVIVC), and population pharmacokinetic/pharmacodynamic (PK/PD) modeling. This approach enables the prediction of both plasma concentration–time and pharmacodynamic response–time profiles directly from formulation composition. Using ticagrelor as a model drug, nineteen sustained-release formulations were prepared and characterized in vitro based on a mixture design with three formulation variables. Three formulations spanning fast, medium, and slow dissolution rates were selected for in vivo pharmacokinetic and pharmacodynamic evaluation in beagle dogs. In vitro dissolution kinetics were described using a Michaelis–Menten model, and the maximum dissolution rate (Vmax) was used as a common linking parameter across the DoE, IVIVC, and PK/PD components. A population PK/PD model incorporating time-dependent dissolution and site-dependent absorption processes was established, and a Level A IVIVC was developed by correlating in vitro and in vivo Vmax values. The framework was validated using both internal and external formulations and successfully predicted pharmacokinetic and pharmacodynamic profiles from formulation composition alone. Prediction errors were within 12.70% for internal validation formulations and within 9.67% for an additionally prepared external validation formulation, meeting FDA criteria for IVIVC predictability. This framework provides a mechanistically grounded strategy for model-informed optimization of sustained-release tablet delivery systems.
SN - 1071-7544
SN - 1521-0464
ER -