Manufacturing & Analytical Characterization
Maksim Khotimchenko, PhD
Principal Scientist, DMPK Scientific Advisory
Catalent
San Diego, California
The presentation entitled “Leveraging PBPK Modeling to Guide Successful Formulation Development” offers a comprehensive exploration of how physiologically based pharmacokinetic (PBPK) modeling transforms the landscape of drug development. Designed for scientists, formulation experts, and decision-makers in pharmaceutical R&D, the session provides both foundational knowledge and practical insights, illustrated with real-world case studies.
The talk opens by framing the critical role of PBPK modeling in modern drug development. It contrasts traditional pharmacokinetic (PK) approaches, such as empirical, non-compartmental, and compartmental modeling with advanced computational and mechanistic methods, including AI/ML-based and PBPK modeling. The limitations of empirical approaches are discussed, particularly their reliance on extensive experimental data and lack of mechanistic understanding. In contrast, PBPK modeling is presented as a powerful, mechanistic tool that integrates biological, chemical, and mathematical data to simulate drug behavior, optimize dosing strategies, and reduce reliance on costly and time-consuming experimental trials.
A core theme is the “Right First Time” approach to molecule developability assessment. The presentation details how early-stage characterization, covering solubility, permeability, metabolic stability, and operational considerations, enables informed decision-making. By defining the problem statement before formulation, teams can challenge assumptions, optimize molecule selection, and streamline the development process. The importance of integrating physicochemical and DMPK (ADME) data is emphasized, ensuring that formulation strategies are grounded in robust scientific evidence.
The session delves into the fundamentals of PBPK modeling, explaining how it differs from traditional PK by predicting absorption rates based on compound properties and physiological parameters, rather than relying solely on empirical fits. The gastrointestinal tract is explored in detail, with attention to absorption sites, transit times, and the impact of formulation on bioavailability. The presentation introduces leading PBPK software tools, such as GastroPlus®, and explains the ACAT model’s compartmental approach to simulating oral absorption.
Real-world case studies illustrate the practical application of PBPK modeling. Examples include candidate selection during lead optimization, where simulated exposures are compared with measured profiles to validate in vitro data and predict human pharmacokinetics. The presentation demonstrates how PBPK analysis can reveal the root causes of suboptimal bioavailability - whether due to poor solubility, low permeability, or high first-pass loss, and guide the selection of enabling formulations or alternative dosing routes. Modified release strategies, intraoral and intranasal delivery, and the use of PBPK-driven simulations to minimize animal studies and accelerate human trials are all discussed.
The presentation concludes with a synthesis of key messages: PBPK modeling enhances understanding of absorption and metabolism barriers, enabling targeted formulation strategies. It supports candidate selection, reduces development risks and costs, and facilitates regulatory acceptance by providing data-driven insights.
Attendees will leave with a clear understanding of how PBPK modeling empowers data-driven decisions, optimizes formulation development, and accelerates the path to successful clinical outcomes. This session is helpful for anyone seeking to leverage advanced modeling to drive innovation and efficiency in pharmaceutical development.