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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15min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(11168±2395)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。
OBJECTIVE: To study in vivo and in vitro correlations of aniracetam self-emulsifying agents with conventional tablets and to evaluate their in vivo pharmacokinetics for oral administration in rats. Methods: The release characteristics of self-emulsifying preparations and ordinary tablets were determined by in vitro dissolution test. The concentrations of active metabolites in the plasma were determined by RP-HPLC. The in vivo absorption was calculated by Wagner-Nelson method Score (f) The correlation between absorption fraction (f) of two formulations and cumulative in vitro dissolution (Q%) was studied. Results: The dissolution rate of the self-emulsifying microemulsion after 15 min was (80 ± 4)%, which was significantly higher than that of the tablet (50%). The recovery rate of the metabolites in vivo was 90% % And 6%, the method of high sensitivity, accurate and reliable. The AUC0-∞ of self-emulsifying microemulsion was (11168 ± 2395) ng.mL-1.h, which was three times higher than that of the normal tablet. The MRT0-∞ of self-emulsifying microemulsion and tablet were (2.7 ± 0.6) h and (1.7 ± 0.5) h, respectively, with statistical difference (P <0.05). The in vitro and in vivo correlation results showed that the in vivo absorption of the tablets was linearly correlated with the in vitro dissolution, the slope of the linear equation was 0.7765 and the intercept was -2.9527. The in vitro and in vivo correlation of the self-emulsifying microemulsion fitted the quadratic model, The coefficient is 0.972. Conclusion: Aniracetam self-emulsifying drug delivery system can significantly improve the bioavailability of drugs in vivo. Self-emulsifying formulations containing absorption promoting composite surfactant and oil phase, the drug in vitro showed a rapid release of the characteristics of spontaneous and gastrointestinal fluid form o / w microemulsion after the lymphatic transport of the absorption pathway.