盐酸帕罗西汀肠溶缓释片的研制及体外释放度和体内药物动力学评价

Preparation and evaluation in vitro release and in vivo pharmacokinetic of paroxetine hydrochloride enteric-coated sustainedrelease tablets

目的研制盐酸帕罗西汀肠溶缓释片,研究其体外释放及人体药物动力学参数。方法以羟丙甲纤维、山嵛酸甘油酯为缓释材料,用双层压片及肠溶包衣工艺制备缓释片。以高效液相色谱法进行体外释放测试,采用f2相似因子法评价自制制剂和参比制剂的体外释放曲线,并研究了参比制剂及两批不同处方的自制制剂在14名健康志愿者中的单剂量药物动力学。结果两个自制制剂和参比制剂体外释放试验f2相似因子大于50,相对生物利用度分别为108.70%和146.82%。结论研制的盐酸帕罗西汀肠溶缓释片具有缓释特性,其中一个自制制剂在扩大样本量后可达到和参比制剂生物等效,另一个和参比制剂无法生物等效。体外释放和体内吸收具有一定的相关性,但f2结果不能反映盐酸帕罗西汀肠溶缓释片的体内生物等效性。

Objective To prepare enteric-coated sustained-release tablets of paroxetine hydrochloride,and evaluate its in vitro release and pharmacokinetic parameters.Methods Hypromellose and glyceryl behenate were used to prepare sustained release tablets by application of double compression and enteric coating technology.In vitro release was detected by HPLC,and the release behavior similarity was investigated by comparison between the reference and self-prepared tablets.Similar factor f2 was used to evaluate the similarity of release curves.A single-dose tablets of reference and two batches of self-made preparations with different formulations were given to 14 healthy volunteers,and pharmacokinetic parameters were estimated.Results The in vitro release data of the two self-made preparations and the reference showed that the f2 was more than 50,and the relative bioavailability was 108.70%and 146.82%,respectively.Conclusions The formulated paroxetine hydrochloride entericcoated sustained-release tablets exhibit sustained release characteristics in vivo.The result suggests that one of the self-made preparations will be bioequivalent with the reference if increase the test sample,while the other self-made preparation cannot be bioequivalent.There existed correlation between the in vitro release and in vivo absorption of paroxetine hydrochloride enteric sustained-release tablets,but the f2 can not be used to evaluate the bioequivalence.