氯诺昔康凝胶剂的研制

摘要

Purpose To prepare Lornoxicam gel and to study its release and permeation ability in vitro. Methods The apparent solubility and oil-water partition coefficient of drugs were determined by UV method. The permeation in vitro was carried out by a two-compartment diffusion cells with mouse skin and cellophane as barriers. By taking its 6-hour accumulative penetration amount as index the factors such as the concentration of carbomer, azone, propylene glycol were investigated by an orthogonal design, and thus the best formula could be obtained. The local irritative response of Lornoxicam gel were also measured.Results The apparent solubility of Lornoxicam was 8.65 μg/mL in distilled water and 86.0,324.0 μg/mL in phosphate buffered solution with pH values of 6.8,7.4 and its oil-water partition coefficient was 1.52. The optimal formulation of Lornoxicam gel contained 0.75％ carbomer,30％ propylene glycol and 4％ azone. The gel had suitable viscosity and pH was 6.8-7.0. The process of percutaneous permeation of Lornoxicam gel in vitro conformed to zero order equation. No irritation reactions like blister, rash,redness and swelling occurred in the skin after applying Lornoxicam gel. Conclusion Lornoxicam transcutaneous gel can be prepared simply. Its quality is controllable.%目的:制备氯诺昔康凝肢剂,考察其体外经皮渗透性.方法:采用紫外分光光度法测定氯诺昔康的表观溶解度和油水分配系数.采用Franz扩散池考察载药凝胶剂的体外经皮渗透性,以6h累积渗透量为指标,采用正交试验设计筛选最佳处方,探讨了卡渡姆浓度、氮酮及丙二醇用量对氯诺昔康凝胶剂经皮渗透的影响,并考察其局部刺激性.结果:氯诺昔康在水、pH6.8和pH7.4磷酸盐缓冲液中的表现溶解度分剐为8.65,86.0和324.0μg/mL,油水分配系数为1.52;正交试验优化的最佳处方为:舍0.75%卡波姆、30%丙二醇、4%月桂氮卓酮.制备的凝胶剂外观细腻,黏度适宜,pH值为6.8-7.O,体外经皮渗透实验结果符合零级动力学方程,家兔各涂药部位无水疤、疹块、红肿等现象.结论:氯诺昔康凝胶剂制备工艺简单,质量可控.