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ORIGINAL RESEARCH article

Front. Med. Technol.
Sec. Pharmaceutical Innovation
Volume 7 - 2025 | doi: 10.3389/fmedt.2025.1499189

Bioanalytical Method development, in-vivo pharmacokinetic evaluation, exvivo platelet aggregation inhibition activity of a novel solid dispersion formulation of Ticagrelor

Provisionally accepted
Abhishek Srivastava Abhishek Srivastava 1*Simrata Bedi Simrata Bedi 2*Abhishesh Kumar Mehata Abhishesh Kumar Mehata 3Datta Maroti Pawde Datta Maroti Pawde 4*Ketan Vinayakrao Hatware Ketan Vinayakrao Hatware 4*Mohammad Ahmad Khan Mohammad Ahmad Khan 1*M.S. Muthu M.S. Muthu 3*Uma Bhandari Uma Bhandari 1*
  • 1 Jamia Hamdard University, New Delhi, National Capital Territory of Delhi, India
  • 2 Sun Pharma Industries Limited, Princeton, New Jersey, United States
  • 3 Indian Institute of Technology (BHU), Varanasi, India
  • 4 SVKM's Narsee Monjee Institute of Management Studies, Mumbai, Maharashtra, India

The final, formatted version of the article will be published soon.

    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. An in-vivo 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.

    Keywords: ticagrelor, Antithrombotic agent, Solid dispersion, bioavailability, pharmacokinetic

    Received: 20 Sep 2024; Accepted: 15 Jan 2025.

    Copyright: © 2025 Srivastava, Bedi, Mehata, Pawde, Hatware, Khan, Muthu and Bhandari. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence:
    Abhishek Srivastava, Jamia Hamdard University, New Delhi, 110062, National Capital Territory of Delhi, India
    Simrata Bedi, Sun Pharma Industries Limited, Princeton, NJ 08540, New Jersey, United States
    Datta Maroti Pawde, SVKM's Narsee Monjee Institute of Management Studies, Mumbai, 400056, Maharashtra, India
    Ketan Vinayakrao Hatware, SVKM's Narsee Monjee Institute of Management Studies, Mumbai, 400056, Maharashtra, India
    Mohammad Ahmad Khan, Jamia Hamdard University, New Delhi, 110062, National Capital Territory of Delhi, India
    M.S. Muthu, Indian Institute of Technology (BHU), Varanasi, India
    Uma Bhandari, Jamia Hamdard University, New Delhi, 110062, National Capital Territory of Delhi, India

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.