DESIGN, OPTIMIZATION, AND CHARACTERIZATION OF A NOVEL AMORPHOUS SOLID DISPERSION FORMULATION FOR ENHANCEMENT OF SOLUBILITY AND DISSOLUTION OF TICAGRELOR

作者：A. K. Srivastava, Mohammad Ahmed Khan, Simrata Bedi, Uma Bhandari · 发表于：International Journal of Applied Pharmaceutics · 年份：2023 · DOI：10.22159/ijap.2023v15i4.47618 · 被引用次数：8 · 研究领域：Drug Solubulity and Delivery Systems、Advanced Drug Delivery Systems、Intramuscular injections and effects

Objective: The study aims to enhance the solubility and dissolution of ticagrelor by formulating an amorphous solid dispersion using the hot melt extrusion technique. Methods: Solubility of ticagrelor is very limited in water and buffers of pH 1.2 to 6.8, which is one of the prime reasons for its low oral bioavailability. Amorphous solid dispersions were prepared using the Hot Melt Extrusion technique using different polymers, plasticizers, and surfactants. The formulation is optimized based on the level of polymer in the formulation. The final formulation of Ticagrelor Amorphous Solid Dispersion is made with a drug-polymer ratio of 1:3, keeping the plasticizer level at 10% of the polymer along with a surfactant Sodium Lauryl Sulfate. Results: The formulation showed an increase in solubility of 193.95-times in water, 50.71-times in 0.1 N HCl, 332.74-times in pH 4.5 acetate buffer, and 85.20-times in pH 6.8 phosphate buffer as compared to the pure drug. The drug release of the final formulation was found to be 70.0±4.4%, 55.4±1.1%, 35.5±2.1%, and 30.0±0.8% at 90 min, while the reference product showed a release of 9.4±1.1%, 20.7±0.5%, 8.4±0.3%, and 7.8±0.2% at 90 min in water, 0.1 N HCl, pH 4.5 acetate buffer and pH 6.8 Phosphate Buffer respectively. The drug release of the final formulation was found to be 99.1±3.8% at 60 min in 0.2% w/v Polysorbate-80 in water. Conclusion: In the present study, the amorphous solid dispersion of the poorly-soluble drug ticagrelor was successf...