吲哚美辛乳膏的制备及体外透皮特性和药效学研究

发布时间：2018-03-16 05:03

  本文选题：吲哚美辛　切入点：乳膏　出处：《辽宁医学院》2015年硕士论文　论文类型：学位论文

【摘要】：目的采用正交设计法优化乳膏剂处方,制备吲哚美辛乳膏。建立吲哚美辛乳膏体外释放度的测定方法。考察自制吲哚美辛乳膏剂的质量和稳定性。考察吲哚美辛乳膏剂的镇痛消炎作用及是否具有皮肤刺激性。方法以吐温80、单硬脂酸甘油酯、液体石蜡、凡士林的用量为考察对象,以乳膏剂外观性状、离心试验及耐热耐寒试验是否分层为指标,采用正交设计法优化乳膏剂处方。以立式扩散池为实验装置、以小鼠腹部皮肤为渗透屏障、以20%乙醇-p H 7.4缓冲液为接受液,并采用HPLC法测定乳膏在释放介质中的累积渗透量。对自制乳膏剂的外观性状、p H、粒度以及均匀性进行检查,对药品含量进行测定,并考察样品的稳定性。以小鼠为实验对象考察吲哚美辛乳膏的镇痛消炎作用;以家兔为实验对象,分别进行了单次及多次给药的皮肤刺激性试验。结果经过单因素和正交设计试验优化得到的最佳处方是吐温80 0.45 g,单硬脂酸甘油酯0.9 g,液体石蜡0.9 g,凡士林0.6 g,按照最优处方制备3批吲哚美辛乳膏进行验证,乳膏在6 000 r·min-1离心20 min,在55℃的恒温箱中放置6 h,在-20℃的冰箱中放置24 h,结果3批乳膏的外观无任何变化。将吲哚美辛乳膏的累积渗透量对时间进行线性回归,回归方程为Q=5.6436t+12.1370,r=0.9906,表明吲哚美辛乳膏的累积渗透量与时间呈良好的线性关系,乳膏具有良好的渗透性能。通过对乳膏剂的质量及稳定性考察,结果显示乳膏剂的各项检查指标均符合规定标准。通过小鼠对乳膏镇痛抗炎作用的考察,证实乳膏有明显的镇痛消炎作用,通过家兔单次及多次给药的皮肤刺激性试验,试验结果显示吲哚美辛乳膏无皮肤刺激性。结论采用正交设计法优选出了乳膏剂处方,成功的制备了吲哚美辛乳膏,色泽均匀、质地细腻、便于涂布。吲哚美辛乳膏的累积渗透量与时间呈良好的线性关系且渗透性能良好,累积渗透量的测定方法简单可靠。自制样品的外观性状、p H、粒度、均匀性、药品含量、稳定性均符合规定标准。吲哚美辛乳膏具有很好的镇痛消炎作用且无皮肤刺激性,达到了实验预期的设计目的。
[Abstract]:Objective to optimize the formulation of cream by orthogonal design. To prepare indomethacin cream. To establish a method for determining the release rate of indomethacin cream in vitro. To investigate the quality and stability of indomethacin cream. To investigate the analgesic and anti-inflammatory effect of indomethacin cream and whether it has skin. Method Twain 80, glycerol monostearate, The dosage of liquid paraffin and vaseline was used as the object of investigation. Taking the appearance character of cream, the stratification of centrifugal test and heat tolerance test as indexes, the formulation of cream was optimized by orthogonal design method. The vertical diffusion pool was used as experimental device. The abdominal skin of mice was used as the permeation barrier, the 20% ethanol-pH 7.4 buffer solution was used as the receiving solution, and the cumulative permeation of the cream in the release medium was determined by HPLC method. The appearance, particle size and uniformity of the self-made cream were examined. The analgesic and anti-inflammatory effects of indomethacin cream on mice and rabbits were investigated. The skin irritation tests of single and multiple doses were carried out respectively. Results the optimum prescription was Tween 800.45 g, glycerol monostearate 0.9 g, paraffin 0.9 g, vaseline 0.6 g. Three batches of indomethacin cream were prepared according to the optimal prescription. The cream was centrifuged at 6 000 r 路min-1 for 20 min, placed in the incubator at 55 鈩，

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