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目的 研制褪黑素HPMC骨架缓释片。并且研究缓释片的药物动力学及生物利用度。方法 以HPMC为骨架制备褪黑素缓释片。考察褪黑素的颗粒大小 ,片剂中HPMC的种类及含量 ,片剂大小 ,填充物的种类及数量 ,压片力等影响药物释放度的因素。采用HPLC荧光检测器测定家犬静脉注射及口服褪黑素后的血药浓度。结果 褪黑素静脉注射后体内血药浓度符合双隔室模型。静注两种剂量后AUC与剂量成正比 ,生物半衰期分别为 6 7 7分和 84 6分 (P >0 0 5 )。褪黑素缓释片相对于常释胶囊的生物利用度为 83 8%。缓释片及常释胶囊的绝对生物利用度分别为 3 75 %及 4 4 9%。结论 褪黑素缓释片具有良好的缓释特性。褪黑素缓释片及常释胶囊的绝对生物利用度都较低 ,缓释片的生物利用度低于常释胶囊但体内平均滞留时间显著长于常释胶囊。缓释片的体外释放与体内吸收速度有良好的相关性。
Objective To develop melatonin HPMC matrix sustained-release tablets. The pharmacokinetics and bioavailability of sustained-release tablets were also studied. Methods HPMC was used as matrix to prepare melatonin sustained-release tablets. Investigate the particle size of melatonin, the type and content of HPMC in the tablet, the size of the tablet, the type and amount of the filler, the tablet force and other factors that affect the drug release. HPLC fluorescence detector was used to determine the blood concentration of rabbits after intravenous injection and oral melatonin. The results of intravenous melatonin in vivo plasma concentration in line with the double compartment model. After intravenous injection of two doses of AUC dose-proportional, biological half-life of 67.7 points and 846 points (P> 0.05). The bioavailability of melatonin sustained release tablets relative to the regular release capsules was 83 8%. The absolute bioavailability of extended release tablets and regular release capsules were 375% and 449%, respectively. Conclusion Melatonin sustained-release tablets have good sustained-release properties. The absolute bioavailability of melatonin sustained release tablets and regular release capsules are low, the bioavailability of sustained release tablets is lower than the regular release capsules but the average residence time in the body is significantly longer than the ordinary release capsules. Sustained-release tablets in vitro release and absorption rate in vivo have a good correlation.