Bioanalytical Method Development, Pharmacokinetic Evaluation, Platelet Aggregation Inhibition Activity of a Novel Solid Dispersion Formulation of Ticagrelor

Overview

Journal Front Med Technol

Specialty Biomedical Engineering

Date 2025 Feb 21

PMID 39981355

Authors

Abhishek Srivastava

Simrata Bedi

Abhishesh Kumar Mehata

Datta Maroti Pawde

Ketan Vinayakrao Hatware

Mohammad Ahmad Khan

M S Muthu

Uma Bhandari

Affiliations

Soon will be listed here.

Abstract

Background: Ticagrelor, a potential antithrombotic drug indicated for cardiovascular events with acute coronary syndrome, has been restricted from its oral use due to poor aqueous solubility. The present investigation aimed to develop validated bioanalytical method for the analysis of plasma samples for improving the oral bioavailability of Ticagrelor. Additionally, evaluation of the improved antiplatelet activity of the Ticagrelor formulation compared to the marketed formulation.

Methods: A bioanalytical method was developed in rat plasma samples using the isocratic separation mode. Plasma samples were processed by liquid-liquid extraction and analyzed by using reverse phase HPLC. A validated method was used for evaluating the pharmacokinetic profile of the developed formulation and marketed formulation in Sprague Dawley rats. Additionally, the ex-vivo antiplatelet aggregation activity was evaluated.

Results: The developed method was accurate and linear (100 ng-800 ng) to quantify the drug in plasma. pharmacokinetic study was conducted for formulation at 10 mg/kg and different pharmacokinetic parameters were evaluated. From the results, we observed∼64% enhancements in the oral bioavailability of the Ticagrelor relative to the marketed formulation. The developed formulation (SD1) showed more significant inhibition of ADP-induced platelet aggregation compared to the marketed ticagrelor (RLD) formulation.

Conclusion: In conclusion, we have successfully developed a validated analytical method for estimating Ticagrelor plasma concentration. Additionally, our study successfully enhanced Ticagrelor's oral bioavailability, and the developed formulation has more significant inhibition of ADP-induced platelet aggregation relative to the marketed formulation, indicating its substantial therapeutic potential.

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