Bioanalytical method development, in-vivo pharmacokinetic evaluation, ex-vivo platelet aggregation inhibition activity of a novel solid dispersion formulation of ticagrelor
BackgroundTicagrelor, 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 f...
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Frontiers Media S.A.
2025-02-01
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| Series: | Frontiers in Medical Technology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fmedt.2025.1499189/full |
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| author | Abhishek Srivastava Abhishek Srivastava Simrata Bedi Abhishesh Kumar Mehata Datta Maroti Pawde Ketan Vinayakrao Hatware Mohammad Ahmad Khan M. S. Muthu Uma Bhandari |
| author_facet | Abhishek Srivastava Abhishek Srivastava Simrata Bedi Abhishesh Kumar Mehata Datta Maroti Pawde Ketan Vinayakrao Hatware Mohammad Ahmad Khan M. S. Muthu Uma Bhandari |
| author_sort | Abhishek Srivastava |
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| description | BackgroundTicagrelor, 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.MethodsA 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.ResultsThe 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.ConclusionIn 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. |
| format | Article |
| id | doaj-art-203a0e3505fe4c8ab27b0527429cd01d |
| institution | Kabale University |
| issn | 2673-3129 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Medical Technology |
| spelling | doaj-art-203a0e3505fe4c8ab27b0527429cd01d2025-02-06T05:21:40ZengFrontiers Media S.A.Frontiers in Medical Technology2673-31292025-02-01710.3389/fmedt.2025.14991891499189Bioanalytical method development, in-vivo pharmacokinetic evaluation, ex-vivo platelet aggregation inhibition activity of a novel solid dispersion formulation of ticagrelorAbhishek Srivastava0Abhishek Srivastava1Simrata Bedi2Abhishesh Kumar Mehata3Datta Maroti Pawde4Ketan Vinayakrao Hatware5Mohammad Ahmad Khan6M. S. Muthu7Uma Bhandari8Formulation Research and Development, Sun Pharmaceutical Industries Ltd, Gurugram, IndiaDepartment of Pharmacology, SPER, Jamia Hamdard University, New Delhi, IndiaFormulation Research and Development, Sun Pharmaceutical Industries Ltd, Gurugram, IndiaDepartment of Pharmaceutical Engineering and Technology, IIT, BHU, Varanasi, IndiaDepartment of Pharmaceutical Sciences, School of Health Sciences and Technology, Dr. Vishwanath Karad MIT World Peace University, Pune, IndiaSchool of Pharmacy & Technology Management, SVKM’S NMIMS Deemed-to-be University, Shirpur, IndiaDepartment of Pharmacology, SPER, Jamia Hamdard University, New Delhi, IndiaDepartment of Pharmaceutical Engineering and Technology, IIT, BHU, Varanasi, IndiaDepartment of Pharmacology, SPER, Jamia Hamdard University, New Delhi, IndiaBackgroundTicagrelor, 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.MethodsA 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.ResultsThe 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.ConclusionIn 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.https://www.frontiersin.org/articles/10.3389/fmedt.2025.1499189/fullticagrelorantithrombotic agentsolid dispersionbioavailabilitypharmacokinetic |
| spellingShingle | Abhishek Srivastava Abhishek Srivastava Simrata Bedi Abhishesh Kumar Mehata Datta Maroti Pawde Ketan Vinayakrao Hatware Mohammad Ahmad Khan M. S. Muthu Uma Bhandari Bioanalytical method development, in-vivo pharmacokinetic evaluation, ex-vivo platelet aggregation inhibition activity of a novel solid dispersion formulation of ticagrelor Frontiers in Medical Technology ticagrelor antithrombotic agent solid dispersion bioavailability pharmacokinetic |
| title | Bioanalytical method development, in-vivo pharmacokinetic evaluation, ex-vivo platelet aggregation inhibition activity of a novel solid dispersion formulation of ticagrelor |
| title_full | Bioanalytical method development, in-vivo pharmacokinetic evaluation, ex-vivo platelet aggregation inhibition activity of a novel solid dispersion formulation of ticagrelor |
| title_fullStr | Bioanalytical method development, in-vivo pharmacokinetic evaluation, ex-vivo platelet aggregation inhibition activity of a novel solid dispersion formulation of ticagrelor |
| title_full_unstemmed | Bioanalytical method development, in-vivo pharmacokinetic evaluation, ex-vivo platelet aggregation inhibition activity of a novel solid dispersion formulation of ticagrelor |
| title_short | Bioanalytical method development, in-vivo pharmacokinetic evaluation, ex-vivo platelet aggregation inhibition activity of a novel solid dispersion formulation of ticagrelor |
| title_sort | bioanalytical method development in vivo pharmacokinetic evaluation ex vivo platelet aggregation inhibition activity of a novel solid dispersion formulation of ticagrelor |
| topic | ticagrelor antithrombotic agent solid dispersion bioavailability pharmacokinetic |
| url | https://www.frontiersin.org/articles/10.3389/fmedt.2025.1499189/full |
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