Photochemical Mechanism of Riboflavin-Induced Degradation of Famotidine and a Suggested Pharmaceutical Strategy for Improving Photostability
Photochemical Mechanism of Riboflavin-Induced Degradation of Famotidine and a Suggested Pharmaceutical Strategy for Improving Photostability
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DOI：
10.1002/jps.24689
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发表时间：
2016-02-01
影响因子：
3.8
通讯作者：
Oguchi, Toshio
中科院分区：
文献类型：
--
作者：
Uchida, Atsushi;Onoue, Satomi;Oguchi, Toshio
本研究旨在阐明核黄素光降解法莫替丁（FMT/RF）的机理，并开发一种光化学稳定的FMT/RF制剂。通过紫外-可见光谱分析、活性氧测定和光稳定性测试对RF的光化学性质进行了表征。在大鼠中静脉内给予含有RF（0.01 mg/kg）的FMT（1 mg/kg）制剂后进行药代动力学研究。RF的UV-VIS光谱模式与太阳光光谱部分重叠，光照射RF产生的ROS显著，因此RF具有较高的光反应潜力。在光稳定性试验中，辐照（250 W/m2）后，FMT/RF中FMT的降解速率约为100%。11-比单独的FMT高10倍。自由基清除剂的FMT/RF导致衰减的FMT/RF的光降解，特别是，L-抗坏血酸（维生素C; VC）的FMT/RF显示约。对FMT/RF的光降解有86%的抑制作用。FMT的药代动力学研究表明，在FMT/RF中加入VC（1 mg/kg）对FMT的药代动力学行为无显著影响。这些结果表明ROS介导的光化学反应可能参与了FMT/RF的光降解途径，VC的补充使用可能是提高FMT/RF光稳定性的一种有吸引力的方法。(C)2016年美国药学协会（R）。爱思唯尔公司出版All rights reserved.
The present study aimed to clarify the mechanism of photodegradation of famotidine with riboflavin (FMT/RF), and to develop a photochemically stabilized formulation of FMT/RF. Photochemical properties of RF were characterized by UV-VIS spectral analysis, reactive oxygen species (ROS) assay, and photostability testing. Pharmacokinetic study was conducted in rats after intravenous administration of FMT (1 mg/kg) formulation containing RF (0.01 mg/kg). The UV-VIS spectral pattern of RF partly overlapped with the sunlight spectrum, and ROS generation from photoirradiated RF was remarkable; thus, RF had high photoreactive potential. In the photostability testing, after irradiation (250 W/m(2)), degradation rate for FMT in FMT/RF was ca. 11-fold higher than that in FMT alone. The addition of radical scavengers to FMT/RF led to attenuated photodegradation of FMT/RF; in particular, the addition of L-ascorbic acid (vitamin C; VC) to FMT/RF showed ca. 86% inhibition of the photodegradation of FMT/RF. The pharmacokinetic study on FMT indicated that the addition of VC (1 mg/kg) to FMT/RF had no significant impact on the pharmacokinetic behavior of FMT. These findings suggest that ROS-mediated photochemical reaction would be involved in the photodegradation pathway of FMT/RF, and the complementary use of VC might be an attractive approach to improve the photostability of FMT/RF. (C) 2016 American Pharmacists Association (R). Published by Elsevier Inc. All rights reserved.