摘要
布洛芬是20世纪60年代开发的一种非甾体类解热镇痛消炎药,由于其难溶于水,所以存在吸收和起效慢的问题,生物利用率低,限制了它在临床上的应用。为了解决这一问题,本文将布洛芬原料药微粉化,减小布洛芬颗粒的粒径,增加其比表面积,从而提高其溶出速率及溶解度,以提高其生物利用度。
通过对微粉化制备工艺的筛选,得到最佳制备工艺为:于250ml的锥形瓶中加入浓度为含2%的泊洛沙姆稳定剂的水溶液150ml,将其放置在0-5℃的冰水浴中,在连续式超声的条件下,以1ml/min的速度匀速滴加浓度为0.04g/ml的布洛芬乙醇溶液50ml,当溶液体系变混浊,在低温下静置6小时后,高速离心10min直至完全分离,然后将所得的固体产品再洗涤、高速离心5min,除去上清液,再将得到的产物置于50℃的真空干燥箱中干燥得到最终产品,将所得的固体产品研磨过筛,即可得到所需要的布洛芬微粉。
通过对布洛芬原料药和微粉不同片剂体外溶出情况的考察,结果表明由布洛芬微粉制备成的普通片和缓释片在不同的溶出介质中的累积溶出率都远远大于由布洛芬原料药制备的片剂,并且由微粉制备的片剂在各种溶出介质中,在一定的时间内累计溶出率能达到或接近80%以上,溶出情况良好。对缓释片在不同溶出介质中的体外释药情况分别进了零级方式、一级方式、Higuchi方式拟合,结果表明其释药规律都符合Higuchi方程。
Ibuprofen is a kind of non-steroidal antipyretic、analgesic and anti inflammatory drugs, which was developed in 1960s.It is a kind of water-insoluble drug, as it is hard to dissolve in water, so there is the problem of low absorption、low bioavailability and low effect speed. The application in clinical medicine is limited. To solve this problem, in this research, raw ibuprofen is micronized so as to reduce particle size and increase the specify surface area, which is beneficial to enhance its dissolution and solubility, further to improve the bioavailability.
By screening of the micronized preparation technique, the best preparation: put the 250ml conical beaker, adding 150ml poloxamer solution with 2% concentration as the stabilizer, into the ice-water bath at 0-5℃.In conditions of continuous ultrasound, dropping 50ml ibuprofen ethanol solution with 0.04g/ml concentration at 1ml/min uniform dropping rate. when the aqueous solution become turbid, standing for 6 hours at low temperature. With 10min high-speed centrifugation until solid product is completely separated from the aqueous solution, then re-washed and high-speed centrifugation 5min, remove the supernatant solution. Solid product is placed in vacuum drying oven at 50℃,then grounded and sieved by mesh.
Through the investigation of the dissolution of different ibuprofen tablets, the results show that the accumulation dissolution rate in various dissolution media of two kinds ibuprofen micronization tablets is much larger than the ibuprofen raw material tablets. The accumulation dissolution rate of tablets that are produced with ibuprofen micronization can reach nearly 80% in a certain period of time. The research of the drug release pattern of ibuprofen micronization sustained-release tablets shows that the drug release pattern is consistent with Higuchi equation.
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