卡托普利迟释型缓释片体外释放和体内吸收相关性研究

 目的卡托普利迟释型缓释片的体外释放和体内吸收的比较。方法以0.1 mol·L^-1的盐酸溶液为释放介质,转速 100 r·min^-1,在预定时间取样,HPLC测定卡托普利迟释型缓释片的体外释放度。给Beagle犬交叉服用单剂量卡托普利迟释型缓释片(CDSR)和普通缓释片(CSR),定时抽取血样,采用柱前衍生-固相萃取-HPLC测定血浆样品中卡托普利浓度,以Wagner-Nelson法计算药物的体内吸收百分数。结果迟释型缓释片在体外释放3 h开始起释,5 h时累积释放率仅10％,而普通缓释片1 h即释放20％。Beagle犬服用迟释型缓释片后2 h内血浆中未检测到药物,3～5 h时血药浓度达最大;而普通缓释片服用 0.5 h后血浆中即可检测到药物,1～3 h时血药浓度达最大。结论卡托普利迟释型缓释片的体外释放和体内吸收有一定相关性。

Study on Correlation Between in vitro Release and in vivo Absorption of Captopril Delayed-onset, Sustained Release Tablet

OBJECTIVE To study the correlation between in vitro release and in vivo absorption of captopril delayed-onset, sustained release tablets.METHODS The in vitro release characteristics of captopril delayed-onset, sustained release tablet were evaluated at 0.1 mol·L^-1 hydrochloric acid medium. The results were compared with that of the common delayed tablet. The oral administration absorption in vivo was tested in beagle dogs with a single-dose, crossover study under fasting conditions, comparing the delayed-onset, sustained release tablets (CDSR) and common sustained release tablets(CSR). The fractions absorbed were calculated by the Wagner-Nelson method. The captopril concentration in plasma was determined by a pre-column derivation HPLC with a solid phase extraction. RESULTS The captopril concentration in plasma was not detected until 2 h after the oral administration, and the peak blood level occurred in 3-5 h after an oral administration, in vitro release started at 3.5 h, the accumulate release percent was about 10% at 5 h,the maximum release was reached in 8-10 h,for the delayed-onset, sustained release tablets. While the captopril concentration was detected at 0.5 h after the oral administration, and the peak blood level occurred in 1-3 h after the oral administration, the accumulate release percent in vitro was about 20% at 1 h, for the common delayed tablets. CONCLUSION There are some correlation between release in vitro and absorption of the delayed-onset in vivo,sustained release tablets, and the remarkable lag time is observed,compared with the common delayed tablets.