Aqueous solubility and degradation kinetics of the phytochemical anticancer thymoquinone; probing the effects of solvents, pH and light.
Aqueous solubility and degradation kinetics of the phytochemical anticancer thymoquinone; probing the effects of solvents, pH and light.
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DOI：
10.3390/molecules19055925
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发表时间：
2014-05-08
期刊：
影响因子：
--
通讯作者：
Zhou J
中科院分区：
文献类型：
--
作者：
Salmani JM;Asghar S;Lv H;Zhou J
百里醌（TQ）是一种有效的抗癌植物化学物质，具有体外证实的功效。其临床用途尚未确定，很少有报告记录其配方。尽管这种有价值的药物与体内功效直接相关，但也没有关于其水溶解度和稳定性的报道。在本研究中，我们建立并验证了一种稳定性指示HPLC方法，用于检测TQ及其在不同条件下的降解产物。然后，我们研究了TQ在水溶液中的溶解度和稳定性。稳定性研究旨在确定pH值、溶剂类型和光照对TQ降解过程的影响，沿着该降解动力学研究。TQ在不同水性溶剂中的溶解度不同，并且可能由于稳定性问题而受到损害。然而，这些发现证实，水溶性不是药物制剂的主要障碍，主要是由于相当大的水溶性（>500 μg/mL），如果通过胃肠外途径给药，可能足以发挥药理学作用。稳定性研究结果表明，TQ在所有水溶液中的稳定性特征极低，且随溶剂类型而变化，降解迅速。降解动力学研究表明，pH值对降解过程有显著影响。无论溶剂类型如何，该过程在更酸性和碱性的pH值下遵循一级动力学，在pH 5-7.4下遵循二级动力学。结果还表明，光照对TQ的稳定性影响更大，因为较短的暴露时间导致严重降解，与溶液pH值和溶剂类型无关。我们的研究结果还解决了一些差异，在以前发表的研究有关制定和量化TQ与建议的解决方案。总的来说，目前的研究得出结论，TQ在水溶液中不稳定，特别是在碱性pH值下，除了表现出严重的光敏感性。该数据表明水溶液不适合作为TQ制剂的药物载体。据我们所知，这是第一项描述TQ水溶性和稳定性的研究，可能导致开发稳定有效的TQ制剂。
Thymoquinone (TQ) is a potent anticancer phytochemical with confirmed in vitro efficacy. Its clinical use has not yet established, and very few reports have documented its formulation. There also are no reports about the aqueous solubility and stability of this valuable drug, despite their direct correlation with the in vivo efficacy. In the current research, we have established and validated a stability-indicating HPLC method for the detection of TQ and its degradation products under different conditions. We then investigated the solubility and stability profiles of TQ in aqueous solutions. The stability study was aimed to determine the effect of pH, solvent type and light on the degradation process of TQ, along with the investigation of the kinetics of this degradation. The solubility of TQ varied in different aqueous solvents, and might be compromised due to stability issues. However, these findings confirm that the aqueous solubility is not the major obstacle for the drug formulations mainly due to the considerable water solubility (>500 μg/mL) that may be enough to exert pharmacologic effects if administered via parenteral route. Stability study results showed a very low stability profile of TQ in all the aqueous solutions with rapid degradation that varied with solvent type. The study of the degradation kinetics showed a significant effect of pH on the degradation process. The process followed first order kinetics at more acidic and alkaline pH values, and second order kinetics at pH 5–7.4, regardless of the solvent type. The results also expressed that light has a greater impact on the stability of TQ as a shorter period of exposure led to severe degradation, independent of the solution pH and solvent type. Our results also addressed some discrepancies in previously published researches regarding the formulation and quantification of TQ with suggested solutions. Overall, the current study concludes that TQ is unstable in aqueous solutions, particularly at an alkaline pH, in addition to presenting severe light sensitivity. This data indicates the inappropriateness of aqueous solutions as pharmaceutical vehicles for TQ preparations. To the best of our knowledge, this is the first study describing TQ aqueous solubility and stability that may lead to the development of a stable and effective TQ formulation.
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影响因子：
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DOI：
10.1080/01635581.2010.509832
发表时间：
2010
期刊：
Nutrition and cancer
影响因子：
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DOI：
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发表时间：
2011-07-01
期刊：
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影响因子：
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