Bioanalytical method development, in-vivo pharmacokinetic evaluation, ex-vivo platelet aggregation inhibition activity of a novel solid dispersion formulation of ticagrelor.

IF 2.7 Q3 ENGINEERING, BIOMEDICAL
Frontiers in medical technology Pub Date : 2025-02-06 eCollection Date: 2025-01-01 DOI:10.3389/fmedt.2025.1499189
Abhishek Srivastava, Simrata Bedi, Abhishesh Kumar Mehata, Datta Maroti Pawde, Ketan Vinayakrao Hatware, Mohammad Ahmad Khan, M S Muthu, Uma Bhandari
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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. 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.

背景:替卡格雷(Ticagrelor)是一种潜在的抗血栓药物,适用于急性冠状动脉综合征的心血管事件,但由于水溶性较差,其口服使用一直受到限制。本研究旨在开发用于分析血浆样品的有效生物分析方法,以提高替卡格雷的口服生物利用度。此外,还评估了与市售制剂相比,替卡格雷制剂抗血小板活性的提高情况:方法:采用等度分离模式对大鼠血浆样品进行生物分析。血浆样品经液-液萃取处理后,采用反相高效液相色谱法进行分析。采用经过验证的方法评估了开发制剂和上市制剂在 Sprague Dawley 大鼠体内的药代动力学特征。此外,还评估了体内外抗血小板聚集活性:结果:所开发的方法准确、线性(100 ng-800 ng),可定量检测血浆中的药物。以 10 mg/kg 的剂量对制剂进行了体内药代动力学研究,并评估了不同的药代动力学参数。结果表明,与市售制剂相比,替卡格雷的口服生物利用度提高了 64%。与上市的替卡格雷(RLD)制剂相比,开发的制剂(SD1)对ADP诱导的血小板聚集有更明显的抑制作用:总之,我们成功地开发了一种有效的分析方法来估算替卡格雷的血浆浓度。此外,我们的研究还成功地提高了替卡格雷的口服生物利用度,与市售制剂相比,所开发的制剂对ADP诱导的血小板聚集具有更显著的抑制作用,这表明其具有巨大的治疗潜力。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
CiteScore
3.70
自引率
0.00%
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审稿时长
13 weeks
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