The effect of alginate on in vitro and in vivo behaviors of ticagrelor self-microemulsifying drug delivery system

초록

Ticagrelor (TCG) is a poorly soluble and permeable anti-platelet agent with limited oral bioavailability. To overcome this limitation, a novel oral formulation such as TCG-loaded self-microemulsifying drug delivery system (SMEDDS) showing rapid and improved absorption was developed. In this study, we aimed to control the release of TCG via the formation of TCG-loaded SMEDDS-alginate beads (TSAB) through combining TCG-loaded SMEDDS (TCG-SM) and pH sensitive alginate beads. TSAB exhibited pH-responsive release, with attenuated initial drug release in acidic buffer (pH 1.2) and enhanced release in neutral buffer of pH 6.8, leading to enhanced gastrointestinal absorption. In vitro release kinetics followed the Korsmeyer-Peppas model, indicating a diffusion- and erosion-based mechanism. In vivo pharmacokinetic studies in rats showed a delayed Tmax (4 h) and a significantly increased AUC0-infinity (186.54% relative to Brilinta (R)), demonstrating sustained and improved drug absorption. TSAB also showed a qualitative Level B in vitro-in vivo correlation (IVIVC), as its in vivo absorption pattern aligned well with the in vitro pH-dependent release. The combination of SMEDDS and alginate beads enables site-specific oral delivery of poorly water-soluble drugs by protecting them from gastric degradation, promoting pH-triggered intestinal release, and enhancing systemic exposure through sustained drug release.

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