目的研制灵芝酸单体T(GA-T)片剂,并评价其在兔体内的药动学特性。方法采用单因素法考察药用辅料的种类与用量,优化处方和制备工艺,经粉末直接压片制得GA-T片剂。高效液相色谱法测定GA-T在兔体内的血药浓度,采用药动学软件kinetica5.0计算药动学参数,研究GA-T片剂在兔体内药动学特性。结果GA-T片剂优化处方中,选用微晶纤维素与喷雾干燥乳糖1∶1为填充剂,1%微粉硅胶和0.5%硬脂酸镁分别作为助流剂与润滑剂。制得片剂的外观、硬度、崩解时间和溶出度等各项评价指标均符合《中国药典》2010年版的要求。兔口服GA-T片剂的绝对生物利用度为33.03%。结论粉末直接压片法工艺简单可靠,GA-T片剂兔体内生物利用度良好。本实验为GA-T的临床前研究提供了实验数据。
Abstract
OBJECTIVE To prepare the ganoderic acid T (GA-T) tablets and evaluate the pharmacokinetics and bioavailability in rabbits. METHODS GA-T tablets were prepared by direct powder compression. After investigating the type and amount of excipients by single-factor method, the formulation of GA-T tablets was optimized and prepared by direct powder compression. An HPLC method was used for the determination of plasma concentration in rabbits after administration of GA-T. The main pharmacokinetic parameters were analyzed by pharmacokinetic software kinetica 5.0. The pharmacokinetic characteristics of GA-T tablets were studied. RESULTS In optimization of formulation, microcrystalline cellulose and spray-dried lactose (1∶1) were selected as bulking agent. In addition, 1% of the silica powder and 0.5% magnesium stearate were used as glidant and lubricant, respectively. The prepared tablets were consistent with the requirements of the 2010 edition of Chinese Pharmacopoeia standards, including appearance, hardness, disaggregation and dissolution of the tablets. The absolute bioavailability of oral GA-T tablets was 33.03%. CONCLUSION The direct powder compression is simple and reliable, and the bioavailability of oral GA-T tablets in rabbits is well. This article provided experimental data for preclinical study of GA-T.
关键词
灵芝酸单体T /
粉末直接压片 /
药动学 /
高效液相色谱法
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Key words
ganoderic acid T /
direct powder compression /
pharmacokinetics /
HPLC
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中图分类号:
R944
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参考文献
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TANG W, LIU J W, ZHONG J J, et al. Ganoderic acid T from Ganoderma lucidum mycelia induces mitochondria mediated apoptosis in lung cancer cells. Life Sci, 2006, 80(3):205-211.
XU K, LIANG X, LIU J W, et al. Antimetastatic effect of ganoderic acid T in vitro through inhibition of cancer cell invasion. Proc Biochem, 2010, 45(8):1261-1267.
CHEN X, TAO S L, GAO F, et al. Quantitative determination of ganoderic acid T in rat plasma by a sensitive RP-HPLC method and its application in pharmacokinetic studies. J Chin Pharm Sci(中国药学英文版), 2010, 19: 172-176.
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脚注
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基金
上海市科学技术委员会项目资助(11DZ2260600和10DZ2220500);上海市中药现代化专项项目(08DZ1971900);华东理工大学交叉学科与重大项目培育基金(WY1213013ECUST)
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