重组水蛭素肠溶包衣微丸的制备及体外释放行为考察

Preparation of recombinant hirudin enteric coated-pellets and exploration on its released behaviour in vitro

目的研制重组水蛭素口服肠溶包衣微丸,并对其在不同pH释放介质中的释放行为进行考察,为重组水蛭素口服制剂的研究与开发提供实验依据。方法以羟丙甲基纤维素酞酸酯(HP55)为包衣材料,利用离心造粒机和流化床包衣设备制备重组水蛭素肠溶包衣微丸;采用二喹啉甲酸(BCA)法测定重组水蛭素肠溶包衣微丸的药物含量。结果所制备的重组水蛭素肠溶包衣微丸药物含量质量分数为3.513%。pH梯度释放实验结果表明,所研制的包衣微丸人工胃液中2 h药物仅释放4.98%;pH 5.8释放介质中继续释放,0.5 h释放82.13%,1 h释放95.47%;pH 7.2释放介质中继续释放,0.5 h释放97.53%,1 h释放98.33%。结论重组水蛭素肠溶包衣微丸在人工胃液中几乎不释药,可避免水蛭素被胃蛋白酶所降解;在人工肠液中药物释放快速而且完全,有利于水蛭素在肠道中的吸收。

Objective To prepare recombinant hirudin preparation for oral administration-recombinant hirudin enteric coated-pellet for providing the experimental basis for the study and development of recombinant hirudin oral preparation. Methods The coated-pellets were prepared by using a centrifugal granulator and a fluid-bed coating equipment, the BCA method was adopted to determine hirudin content in enteric coated-pellets and to explore the released behaviour in different pH media. Results The drug content of prepared recombinant hirudin coated-pellets was 3. 513 % （ w ）. The releasing test showed that the drug was released only 4.89 % in the simulated gastric fluid（pH 1.2） in 2 h; the drug cumulative released percentages in the pH 5.8 fluid were 82.13 % in 0.5 h and 95.47 % in 1 h, in the pH 7.2 fluid were 97.53 % in 0.5 h and 98.33 % in 1 h. Conclusions The hirudin cannot be released in the simulated gastric fluid and the recombinant hirudin coated-pellets may protect hirudin from degraded by gastricsin. However, the drug may be released quickly and completely from coated-pellets in the simulated intestinal fluid, which contributed to absorption of recombinant hirudin.