非洛地平-美托洛尔复方贴剂的透皮吸收促进剂优化

Optimization penetration enhancers for felodipine and metoprolol transdermal patch

目的:优化复合透皮吸收促进剂,制备非洛地平-美托洛尔复方贴剂,并对其外观、物理特性、体外药物释放和经皮渗透性能进行综合评价。方法:以药物体外释放速率和稳态透皮速率为指标,通过正交设计试验考察桉叶油醇、月桂氮卓芯酮和丙二醇体系对贴剂质量的影响,优选最佳复合透皮吸收促进剂构成。结果:优选的透皮吸收促进剂最佳含量分别为桉叶油醇5%、月桂氮芯卓酮3%和丙二醇12%,以该促透体系制备的贴剂药物体外释放速率和稳态透皮速率高,外观和理化特性较佳,物理黏性适宜,各指标均达到预期设计要求。结论:桉叶油醇-月桂氮芯卓酮-丙二醇(5∶3∶12)复合体系对非洛地平和美托洛尔的协同促透作用显著,且稳定可靠,是非洛地平-美托洛尔复方贴剂的优良透皮吸收促进剂。

OBJECIFIVE To optimize the compound penetration enhancers of felodipine -metoprolol transdermal patch and to evaluate the appearance, physico-chemical characteristics, drug release and permeation through rat skin in vitro of the patch. METHODS An orthogonal design was performed to optimize the compound penetration enhancers with the drug release and permeate rate in vitro of the patch as parameters of investigation, and with eucalyptol, azone, and propylene glycol as factors. RESULTS The optimized compound penetration enhancers that satisfied the demands of original design were as follows： 5% of eucalyptol, 3% of azone, and 12% of propylene glycol. Felodipine-metoprolol transdermal patches prepared by using the opti- mal compound penetration enhancers are good in appearance, physico-chemical characteristics and physical viscosity, and posses high drug release and permeating rate in vitro. CONCLUSION The compound penetration enhancers of eucalyptobazone-propylene glycol（5：3： 12） which exhibit evident, stable and reliable synergism in the penetration enhancement of both felodipine and metoprolol are suitable for felodipine-metoprolol transdermal patch.