布洛芬滴丸的成型工艺及体外溶出度研究

Study on the Formation Technology and Dissolution in vitro of Ibuprofen Dropping Pills

目的:研究布洛芬滴丸的成型工艺并测定其体外溶出度。方法:在单因素试验的基础上,采用响应面法,以圆整度、载药率、丸重差异为评价指标,筛选成型工艺中的药物与基质质量比、药液温度、制冷温度;同时进行验证试验,考察最优工艺所制滴丸的体外溶出度并与市售片剂进行比较。结果:布洛芬滴丸的最优成型工艺为药物与基质质量比1∶6,药液温度83℃,制冷温度7.3℃。验证试验中自制滴丸的圆整度为0.945 9、载药率为99.82%、丸重差异为0.040 28,含药量约为30 mg/丸;综合评分的实际值为0.972 5,与理论值(0.980 0)的偏差值为0.771 2%,RSD<1.5%(n=3)。所制滴丸5 min溶出度为25.36%,30 min累积溶出度达到90.12%,与市售布洛芬片剂体外释药行为相似(f_2=54.91),符合一级药动学方程。结论:该成型工艺方法简单、稳定可行;以优化成型工艺所制滴丸可快速释药且重复性好。

OBJECTIVE： To study the formation technology of Ibuprofen dropping pills and determine the dissolution in vitro. METHODS： Based on single factor test and with the spherical degree, drug-loading rate and pill weight variation as the evaluated indexes, response surface methodology was employed to screen the ratios of drug to matrix, drug solution temperatures and cryo- genic temperatures in the formation technology, and verification tests were conducted. The dissolution in vitro of the dropping pills prepared by the optimal technology was investigated and compared with that of the preparations sold in the market. RESULTS： The optimal formation technology of Ibuprofen dropping pills was as follows as the ratio of drug to matrix of 1 ： 6, drug solution temper- ature of 83 % and cryogenic temperature of 7.3 %. In the verification tests, the self-made dropping pills demonstrated a spherical degree of 0.945 9, drug-loading rate of 99.82%, pill weight variation of 0.040 28 and drug-loading capacity of 30 mg/pill, with the actual comprehensive score of 0.972 5, deviating from the theoretical one （0.980 0） by 0.771 2% （RSD〈1.5%, n=3）. The dropping pills prepared had a dissolution rate of 25.36% at 5 min and an accumulated dissolution rate up to 90.12% at 30 min, sim- ilar with the Ibuprofen tablets sold in the market in drug release in vitro （f2=54.91）, conforming to a first-order kinetic equation. CONCLUSIONS： The optimized formation technology is simple, stable, feasible and well reproducible, and the dropping pills which are prepared by such technology can release drug quickly.