茴拉西坦自乳化给药系统与片剂的药代动力学及体内外相关性的研究

中国临床药理学与治疗学 ›› 2007, Vol. 12 ›› Issue (4): 434-439.

茴拉西坦自乳化给药系统与片剂的药代动力学及体内外相关性的研究

李娟¹, 张燕¹, 王广基²

¹中国药科大学药剂学教研室;²药物代谢与药动学研究中心, 南京210009, 江苏

收稿日期:2007-04-02 修回日期:2007-04-20 发布日期:2020-10-30

Pharmacokinetics and in vitro-in vivo correlation evaluation of selfemulsifying drug delivery system and conventional tablets of aniracetam

LI Juan¹, ZHANG Yan¹, WANG Guang-ji²

¹Department of Pharmaceutics, ²Center of Pharmacokinetics, Key Laboratory of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing 210009, Jiangsu, China

Received:2007-04-02 Revised:2007-04-20 Published:2020-10-30
Contact: LI Juan, female, associat e professor, tutor of master,main research field is novel drug delivery system and novel technique.Tel Fax :025-83271766 　E-mail:li juancpu @163.com

摘要/Abstract

摘要： 目的研究茴拉西坦自乳化制剂和普通片剂的体内外相关关系;评价其大鼠口服给药的体内药代动力学。方法通过测定自乳化制剂和普通片剂的体外溶出度考察其释药特性, 采用RP-HPLC 法测定活性代谢产物对氨基甲氧基丁酸的浓度血浆中,通过Wagner-Nelson 法计算体内吸收分数(f), 研究两制剂的吸收分数(f) 与体外累积溶出度(Q %) 的相关性。结果自乳化微乳体外15 min 的溶出度为(80±4) %, 比片剂的溶出度(50 %) 明显提高;体内代谢产物的回收率为90 %, 日内日间精密度分别小于4 %和6 %, 该方法灵敏度高、准确可靠。自乳化微乳的AUC0-∞为(11 168±2 395) ng·mL-1 ·h, 是普通片剂的3 倍。自乳化微乳和片剂的MRT0-∞分别为(2.7±0.6) h和(1.7±0.5) h, 具有统计学差异(P<0.05) 。体内外相关性结果表明, 片剂的体内吸收与体外溶出度呈线性相关, 线性方程的斜率为0.7765, 截距为-2.9527;自乳化微乳的体内外相关性符合二次模型, 其拟合系数为0.972 。结论茴拉西坦自乳化给药系统可显著提高药物体内的生物利用度。自乳化制剂处方中含有促吸收的复合表面活性剂和油相, 其体外药物呈快速释放的特性, 而体内自发与胃肠液形成o w 型微乳后可通过淋巴转运的吸收途径。

关键词: 茴拉西坦, 自乳化给药系统, 对氨基甲氧基基丁酸, 药代动力学, 体内外相关性

Abstract: AIM: To evaluate the correlation between in vitro release and in vivo absorption of aniracetam in conventional tablets and self-emulsifying drug delivery system (SEDDS), to investigate pharmacokinetics of aniracetam self-emulsifying drug delivery system and conventional tablets of aniracetam after oral administration to rats. METHODS: Dissolution behavior of these formulations was evaluated in vitro to assess the properties of dosage forms.And a new RP-HPLC method was developed for the in vivo quantitative determination of 4-p-anisamidobutyric acid (PABA), the active metabolite of aniracetam.To approach the in vitro-in vivo correlation, fraction absorbed in vivo (f) was calculated by Wagner-Nelson method, and then compared with in vitro released drug percentages (Q %). RESULTS: Aniracetam was released rapidly from SEDDS with 80 %±4 %of accumulation dissolution rate compared to that from conventional tablets at 15 min.The recovery of active metabolite of aniracetam was about 90 %, and the intra-days and interday precision were within 4 % and 6 %, respectively.The AUC0-∞ value of aniracetam SEDDS was (11 168±2 395) ng·mL-1 ·h, which was about 3 folds greater than conventional tablets.The parameter MRT0-∞ of aniracetam SEDDS and conventional tablets were (2.7±0.6) h and (1.7±0.6) h, respectively, and the difference was statistically significant(P<0.05).The linear equation of in vitro-in vivo correlation for conventional tablets was obtained by regression as well.Whereas nonlinear correlation was obtained for aniracetam SEDDS, which fitted the quadric model very well and the correlation coefficient was 0.972. CONCLUSION: Aniracetam can be released faster from SEDDS than that from conventional tablets, and SEDDS improved the bioavailability of aniracetam significantly.The SEDDS composed by oil and compound surfactants which could enhance the absorption showed the expressing rate of dissolution, and those formed the o w microemulsion with gastrointestinal liquid could absorb through lymphatic transport route.

Key words: aniracetam, self-emulsifying drug delivery system, 4-p-anisamidobutyric acid, pharmacokinetics, in vitro and in vivo correlation

中图分类号:

R969

李娟, 张燕, 王广基. 茴拉西坦自乳化给药系统与片剂的药代动力学及体内外相关性的研究[J]. 中国临床药理学与治疗学, 2007, 12(4): 434-439.

LI Juan, ZHANG Yan, WANG Guang-ji. Pharmacokinetics and in vitro-in vivo correlation evaluation of selfemulsifying drug delivery system and conventional tablets of aniracetam[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2007, 12(4): 434-439.

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