Work

The Role of In Vitro Model Complexity in Lipid-Based Formulation Screening: A Case Study with Ticagrelor

Year: 2026

Type: article

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.

Source: ACS Omega

DOI: 10.1021/acsomega.6c08404