氢溴酸加兰他敏贴剂体外释药性及经皮渗透性能探究.docVIP

氢溴酸加兰他敏贴剂体外释药性及经皮渗透性能探究 　 作者：邓伟杰，张春凤，赵树进，罗佳波 【摘要】 　　目的 研究氢溴酸加兰他敏贴剂的体外释放和经皮渗透性能。方法 采用Franz扩散池装置和一阶导数光谱法考察氢溴酸加兰他敏贴剂的药物释放性能;采用Franz扩散池装置和高效液相色谱法考察氢溴酸加兰他敏贴剂经离体猪皮的渗透性能。结果 氢溴酸加兰他敏贴剂(1.7 mg·cm-2)24 h累积释放量均超过95%，释放曲线符合Higuchi方程，释放速率为(461.9±41.9) μg·cm-2·h-1/2(n=4);贴剂24 h累积渗透量为(20.904±3.050) μg·cm-2，渗透曲线符合零级动力学方程，透皮速率为(1.270±0.229) μg·cm-2·h-1，透皮时滞为(6.4±0.7) h (n=6)。结论 本研究制备的氢溴酸加兰他敏贴剂具有良好的药物释放性能和一定程度的体外经皮渗透性能。 【关键词】 氢溴酸加兰他敏 贴剂 释放度 经皮渗透 　Abstract:Objective To study the release and transdermal permeation of the transdermal patch of galanthamine hydrobromide in vitro. Methods The release of the transdermal patch of galanthamine hydrobromide was determined by Franz diffusion cells and firstderivative spectrophotometry. The permeation across porcine skin in vitro was studied by Franz diffusion cells and HPLC. Results The cumulative releases of the patches in 24 h (1.7 mg/cm2 ) were all larger than 95%, the release curve was fitted with Higuchi equation, and the release rate was (461.9±41.9) μg/(cm2·h1/2)(n=4). The cumulative permeation of the patches in 24 h was (20.904±3.050) μg/cm2, and the permeation curve was fitted with zeroorder kinetic equation, the permeation rate and the lag time were (1.270±0.229) μg/(cm2·h) and (4±0.7) h (n=6), respectively. Conclusion The transdermal patch of galanthamine hydrobromide had good transdermal release and permeation profile in vitro. 　　Key words:galanthamine hydrobromide; patches; release rate; transdermal permeation 　　氢溴酸加兰他敏(galanthamine hydrobromide)系一种竞争性和可逆性的乙酰胆碱酯酶抑制剂，临床上主要用于治疗脊髓灰质炎、重症肌无力、术后肠肌麻痹、青光眼和阿尔茨海默氏病(Alzheimer’s disease,AD)，也用作解箭毒药和非去极化肌松药的拮抗剂。氢溴酸加兰他敏易透过血脑屏障，其抑制作用时间长且具有选择性，是目前治疗轻、中度AD有效且耐受性良好的药物。口服加兰他敏的不良反应为轻度至中度的胃肠道症状，如恶心、呕吐、腹疼和腹泻，且AD的治疗需要长期给药，因此以加兰他敏为活性成分的透皮治疗系统(Transdermal Therapeutic System,TTS)提供了很好的给药途径。徐子猷等[1]根据氢溴酸加兰他敏的理化性质和药理性质探讨其经皮给药的可能性，同时比较pH值和几种常用促透剂对氢溴酸加兰他敏透皮吸收的影响。赵维娟等[2]研究加兰他敏经皮给药制剂在临床应用的可行性，将其制成透皮吸收乳剂。氢溴酸加兰他敏(商品名：Nivalin)的使用方法有离子导入法[3]：0.25%的氢溴酸加兰他敏溶液在0.20 mA/cm2的电流下通过离子电泳作用透过皮肤到达皮下组织的神经，以治疗外周神经系统疾病。美国专利US570