枸橼酸他莫昔芬缓释片的制备及其体外释药特性

目的：减少枸橼酸他莫昔芬的服用次数，提高病人用药的顺应性。方法：选用HPMCK4M为主要的缓释材料，改变其用量设计6个候选处方，以湿法制颗粒压片制备枸橼酸他莫昔芬缓释片，以药物释放度为标准进行处方筛选。以紫外分光光度法测定药物浓度。按照最优处方制备缓释片，并与市售普通片的释药情况进行对比。结果：在276nm处辅料对枸橼酸他莫昔芬的测定无干扰，该方法的回收率在95％～105％；按最优处方制备的样品在12h释放总药量的86．40％，其释药特性符合零级方程；1h内普通片释放总药量的76．81％，缓释片释放7．08％。结论：采用HPMCK4M为缓释材料制备的枸橼酸他莫昔芬缓释片释药持久而平缓，可维持释放12h以上；较普通片剂有明显缓释作用，有望临床应用。

Development of sustained release tablet of tamoxifen citrate and its in vitro release profile

OBJECTIVE: To reduce the frequency of administration of tamoxifen citrate so as to improve its bioavailability and patients' compliance. METHODS: HPMC(K4M) was employed as major retarded-release controller. The wetting granulation and directly compressing method was used to produce the sustained release tablet. Then the in vitro release profile was applied as main criteria to evaluate six formulations according to the variation of HPMC(K4M) amount. The concentration of tamoxifen citrate was measured by UV spectrometry. Finally the releasing characteristics of sustained release and conventional tablets were compared to clarify the sustained effect of the former. RESULT: At 278 nm there was no interaction between tamoxifen citrate and the recipients so that it was adopted as the wavelength of determination. The recovery efficiency of this method ranged from 95%-105%. The final formulation could release 86.40% of its loading amount in 12 h and its releasing profile fitted the Zero-order equation well. The percentages of accumulative release in 1 h were 76.81% and 7.08% for sustained release tablet and conventional tablet respectively. CONCLUSION: The sustained release tablet of tamoxifen citrate could demonstrate a continuous and stable releasing profile and last for over 12 h. It has significant retarded effect in comparison with the conventional one and could be a new choice of regimen in its clinical application.