熊胆缓释胶囊的溶出度和生物利用度

The Dissolution in Vitro and Bioavaliability of Bear Bile Sustained-release Capsule

为了减少服药次数,方便病人和医护人员,用缓释阻滞剂制备熊胆缓释胶囊。高效液相色谱外标定量法测定熊胆中特有成分熊去氧胆酸(UDCA)的含量,建立校正曲线及方法学考察。用RC-3D溶出仪,转篮法测定12颗胶囊溶出度。家兔16只分成两组,分别灌胃口服熊胆缓释颗粒和熊胆原药100mg/5mL生理盐水液。设定时间点采血后测出血浆中UDCA含量,绘制血药浓时曲线。3P87软件计算曲线峰下面积AUC缓,AUC原和各自的转运速率常数K缓和K原,用公式[AUC缓K缓(/AUC原·K原)]×100%,得出相对生物利用度F。实验结果是(1)体外溶出度按取样时间点为序(h)是05、1、2、4、6、8、10、12、14、16、18、20。累积溶出百分率(%)为1837、2945、3578、4267、4986、5734、6912、7642、8867、9612、9673、9748。(2)血药浓时曲线在设定时间点(h)1、3、6、9、12、24、36、48,缓释组的浓度(μg·mL-1±SD)59159±2748,68826±4279,66278±3964,60207±3717,54964±4459,61480±4775,51573±6009,42462±4522。原药组41334±2291,67522±4635,51498±4987,37518±4175,36644±3933,35464±2986,25870±1914,22318±2693。曲线峰下面积(AUC缓和AUC原)[μg·mL-1·h)]分别是89852664,35164555,两组清除相转运速率常数K缓和K原分别是(h-1)003、0089。(3)计算出相对生物利用度F为7680%。表明熊胆缓释胶囊有好的体外溶出度和较高的体内生物利用度,可提供48h服药一次,达到缓释目的。

In order to decrease taking drug time and favor patients and doctors, nurses, Bear bile Sustained- Release Capsule （BBSRC） was prepared with sustained-release agent. The calibration curve was gained by HPLC with standard Ursodeoxy Cholic Acid （UDCA）. The test of dissolution in vitro was performed by RC-3D dissolution instrument with roling basket for 12 pilles BBSRC. 16 rabbits were derided in two groups and took 100 mg BBSRC and BB by PO separately, UDCA leveling in rabbit blood was determined by HPLC with calibration curve and EXTD. The pharmacokinetic parameters AUC and K10 for two groups with 3P87 computer program were estimated. The bioavailability （F） of BBSRC relativing BB was calculated with F=[AUCBBSRCK10BRSRC/ （AUCBBK10BB） ]×100%. The results were： 1. dissolution curve was percent concentration （%）：18.37,29.45,35.78, 42.67,49.86,57.34,69.12,76.42,88.67,96.12,96.73,97.48; versus time （h） 0.5, 1,2,4,6,8,10,12,14,16, 18,20. 2. UDCA average level in blood of BBSRC group in order time（h）： 1,3,6,9,12,24,36,48 was μg·mL^-1 ： 591.59±27.48,688.26±42.79, 662.78±39.64, 602.07±37.17,549.64±44.59, 614.80±47.75,515.73 ±60.09, 424.62±45.22 ; in BB group ：413.34±22.91, 675.22±46.35, 514.98±49.87,375.18 ±41.75, 366.44±39.33,354.64± 29.86,258.70±19.14,223.18±26.93. Their AUC （μg·mL^-1·h）and （h^-1） were 89 852.664, 35 164.555; 0.03, 0.089 in BBSRC and BB groups separately. 3. The bioavailability（F）of BBSRC relativing BB was 76.80%. BBSRC, which has good release in vitro and height bioavailability in vivo, can be taken one time for 48 h.It is really a sustained release preparation.