DEVELOPMENT OF TICAGRELOR NANOCRYSTALS AS A NOVEL APPROACH FOR ENHANCING SOLUBILITY AND ORAL BIOAVAILABILITY

Abstract

Background: Ticagrelor is a direct-acting, reversible P2Y12 receptor antagonist used in the management of acute coronary syndrome. However, its poor aqueous solubility and limited intestinal permeability contribute to variable oral bioavailability, creating a need for an effective formulation approach to improve its biopharmaceutical performance. Purpose: The present study aimed to develop and optimize ticagrelor nanocrystals using a nanoprecipitation technique to enhance drug dissolution and oral bioavailability. Method: Ticagrelor nanocrystals were prepared using polyvinyl alcohol and polyethylene glycol 6000 as stabilizers. A three-factor, three-level Box–Behnken design with 17 experimental runs was employed to optimize PVA concentration, PEG 6000 concentration, and sonication time based on particle size, zeta potential, and entrapment efficiency. The optimized formulation was characterized by FTIR, DSC, XRD, SEM, and TEM and evaluated for in-vitro dissolution, pharmacokinetic behaviour, and antiplatelet activity. Results: The optimized nanocrystals exhibited a particle size of 231 nm, PDI of 0.281, and zeta potential of −34.1 mV. The optimized nanocrystal formulation demonstrated rapid and enhanced drug dissolution, achieving near-complete drug release within the specified dissolution period. The optimized capsule exhibited satisfactory drug content uniformity, rapid disintegration characteristics, and enhanced in-vitro dissolution performance, indicating improved drug-release efficiency from the capsule dosage form. Pharmacokinetic studies showed increased Cmax (342 ng/mL) and AUC (2280 ng·h/mL).