Enhanced oral bioavailability of ticagrelor via novel cremosomes: Development, characterization, and in-vivo pharmacokinetic evaluation

Citation:
AbouHussein, L. H., Shalaby R. A., Ahmed S., & Fatouh A. M. (2026).  Enhanced oral bioavailability of ticagrelor via novel cremosomes: Development, characterization, and in-vivo pharmacokinetic evaluation. Journal of Drug Delivery Science and Technology. 123, 108528. copy at www.tinyurl.com/22parbbl

ISSN:

1773-2247

Abstract:

Acute Coronary Syndrome (ACS) remains a major global health challenge, requiring rapid and effective antiplatelet therapy. Ticagrelor (TCG), a potent P2Y12 receptor antagonist, suffers from poor aqueous solubility and P-glycoprotein (P-gp)–mediated intestinal efflux, resulting in low and variable oral bioavailability (BCS Class IV). To address these limitations, this study reports the development of novel cerosomes specifically engineered to overcome the P-gp barrier and enhance oral delivery of TCG. Cremosomes were fabricated using the ethanol injection method, combining Span 60, cholesterol, and the P-gp-inhibiting surfactant Cremophor® RH 40. A central composite design was applied to optimize Cremophor RH 40 concentration (Factor A) and cholesterol: drug ratio (Factor B), and to evaluate their effects on particle size (PS), poly-dispersity index (PDI), and entrapment efficiency (EE%). The optimized formulation exhibited a nanoscale PS, narrow size distribution, high EE and a stable negative zeta potential. In-vitro release studies demonstrated sustained drug release under simulated gastrointestinal conditions. In-vivo pharmacokinetic evaluation revealed a significant increase in AUC0–24 and Cmax, with an approximately 344% enhancement in relative oral bioavailability compared to TCG suspension. A significantly reduced mean residence time (MRT) further indicated faster intestinal absorption, consistent with effective P-gp modulation. The optimized cremosomes were successfully incorporated into tablets meeting pharmacopeial standards for hardness, friability, disintegration and drug content. Collectively, this work introduces the first cremosomal tablet platform for TCG, offering a clinically translatable strategy to bypass P-gp efflux, accelerate absorption, and markedly improve oral bioavailability in ACS therapy.

Notes:

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