The Role of In Vitro Model Complexity in Lipid-Based Formulation Screening: A Case Study with Ticagrelor
Abstract
Lipid-based formulations (LBFs) offer a promising strategy to enhance the oral bioavailability of poorly water-soluble drugs, such as biopharmaceutical classification system (BCS) Class IV compounds. However, their in vitro characterization remains challenging because of the complex interplay between dispersion, dissolution, lipid digestion, and absorption. In this study, several LBFs of ticagrelor were investigated using a progressive set of in vitro models of increasing physiological complexity, including dissolution testing in biorelevant media using USP II and USP IV apparatuses, intestinal and gastrointestinal lipolysis assays, and a dynamic gastrointestinal model (TIM-1). The aim of this study was to evaluate the capabilities and limitations of each method and examine how increasing model complexity and experimental setup influences formulation performance and relative ranking. The results showed that the formulation ranking was strongly method-dependent. Under biorelevant conditions, USP II and USP IV generated distinct release kinetics but similar rankings with minimal differences observed between the LBFs. In contrast, lipolysis experiments highlighted the impact of lipid digestion, with the inclusion of a gastric phase increasing intestinal drug availability. TIM-1 provided unique insights into LBF behavior under dynamic gastrointestinal conditions, capturing the combined effects of digestion, transit, and absorption. Overall, the observed model-dependent ranking emphasizes the importance of combining complementary in vitro approaches to achieve a mechanistic and robust characterization of lipid-based formulations and to support future IVIVC development.
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BibTeX
@article{bourdericambon2026role,
title = {{The Role of In Vitro Model Complexity in Lipid-Based Formulation Screening: A Case Study with Ticagrelor}},
author = {Arnaud Bourderi-Cambon and Khaled Fadhlaoui and Manon Rossano and Sandrine Chalancon and Cathérine Dhainaut and Stéphanie Chevrier and Diane Schneider and Sylvain Denis and Philippe Caisse and Eric Beyssac},
journal = {ACS Omega},
year = {2026},
month = sep,
doi = {10.1021/acsomega.6c08404},
url = {https://hal.inrae.fr/hal-05758939v1},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - The Role of In Vitro Model Complexity in Lipid-Based Formulation Screening: A Case Study with Ticagrelor
AU - Arnaud Bourderi-Cambon
AU - Khaled Fadhlaoui
AU - Manon Rossano
AU - Sandrine Chalancon
AU - Cathérine Dhainaut
AU - Stéphanie Chevrier
AU - Diane Schneider
AU - Sylvain Denis
AU - Philippe Caisse
AU - Eric Beyssac
PY - 2026
DA - 2026/09/20
JO - ACS Omega
DO - 10.1021/acsomega.6c08404
UR - https://hal.inrae.fr/hal-05758939v1
AB - Lipid-based formulations (LBFs) offer a promising strategy to enhance the oral bioavailability of poorly water-soluble drugs, such as biopharmaceutical classification system (BCS) Class IV compounds. However, their in vitro characterization remains challenging because of the complex interplay between dispersion, dissolution, lipid digestion, and absorption. In this study, several LBFs of ticagrelor were investigated using a progressive set of in vitro models of increasing physiological complexity, including dissolution testing in biorelevant media using USP II and USP IV apparatuses, intestinal and gastrointestinal lipolysis assays, and a dynamic gastrointestinal model (TIM-1). The aim of this study was to evaluate the capabilities and limitations of each method and examine how increasing model complexity and experimental setup influences formulation performance and relative ranking. The results showed that the formulation ranking was strongly method-dependent. Under biorelevant conditions, USP II and USP IV generated distinct release kinetics but similar rankings with minimal differences observed between the LBFs. In contrast, lipolysis experiments highlighted the impact of lipid digestion, with the inclusion of a gastric phase increasing intestinal drug availability. TIM-1 provided unique insights into LBF behavior under dynamic gastrointestinal conditions, capturing the combined effects of digestion, transit, and absorption. Overall, the observed model-dependent ranking emphasizes the importance of combining complementary in vitro approaches to achieve a mechanistic and robust characterization of lipid-based formulations and to support future IVIVC development.
SN - 2470-1343
ER -