褪黑素双层控释片制备及其在Beagle犬体内的药动学

目的：研制褪黑素双层控释片,并研究其药动学。方法：以羟丙甲基纤维素、硬脂酸为骨架材料,采用固体分散技术和双层压片工艺,制备褪黑素双层控释片。6只Beagle犬随机交叉单剂灌服褪黑素双层控释片(6 mg)或参比制剂(3 mg),以高效液相色谱法测定血浆中褪黑素浓度,3P97程序推算药动学参数。结果：灌服受试制剂和参比制剂后,t_((1/2)ke)分别为(3．3±s0．9)和(1．2±0．5)h,c_(max)分别为(8±5)和(11±4)μg·L~(-1),t_(max)分别为(1．0±0．4)和(0．50±0．20)h,AUC_(0-(?))分别为(38±16)和(25±8)μg·h·L~(-1)。结论：研制的褪黑素双层控释片具有速释和缓释特性。

Preparation of melatonin controlled-release bilayer tablets and its pharmacokinetics in Beagle dogs

AIM:To prepare melatonin controlled-release bilayer tablets and study its pharmacokinetics in Beagle dogs.METHODS:Melatonin controlled-release bilayer tablets were prepared by the solid dispersion method and twice compression technology,using HPMC and stearic acid as the matrix material.In a randomized, crossover design,a single oral dose of melatonin controlled-release bilayer tablets(6 mg)or reference preparation (3mg)was given to 6 beagle dogs,and then plasma concentrations of melatonin were detected by HPLC method with the pharmacokinetic parameters calculated by 3P97 pharmacokinetic program.RESULTS:The t_((1/2)ke),C_(max),t_(max), A UC_(0-t) of test vs reference preparation were(3.3±s 0.9)vs(1.2±0.5)h,(8±5)vs(11±4)μg·L~(-1),(1.0±0.4) vs(0.50±0.20)h,(38±16)vs(25±8)μg·h·L~(-1),respectively.CONCLUSION:The formulated melatonin sustained-release bilayer tablets exhibit sustained release and rapid release characteristics in vitro and in vivo.