不同种类压敏胶及透皮促渗剂对妥洛特罗药物透皮性能的影响  

Effect of various pressure sensitive adhesives and enhancers on the percutaneous absorption of drugs

作　　者：刘辉 陆洋[1] LIU Hui;LU Yang(Beijing University of Chinese Medicine,Beijing 102488)

机构地区：[1]北京中医药大学,北京102488

出　　处：《中南药学》2018年第9期1205-1209,共5页Central South Pharmacy

基　　金：国家科技重大专项(No.2014ZX09301306009)

摘　　要：目的探讨不同种类压敏胶(PSA)、PSA不同官能团及不同透皮促渗剂对妥洛特罗透皮性能的影响。方法通过显微镜观察法测定妥洛特罗在PSA中的溶解度,并利用Franz扩散法考察PSA种类对药物透皮性能的影响;采用模型预测的方法,预测肉豆蔻酸异丙酯(IPM)、二乙二醇单乙基醚(Transcutol P)、单亚油酸甘油脂、氮酮、己二酸二异丙酯等5种促渗剂的促渗效果并利用饱和药物浓度的液体石蜡溶液透皮实验进行验证。结果药物在丙烯酸PSA的溶解度远大于聚异丁烯PSA(DUKO-TAK-6908)及硅酮PSA(BIO-4302);有结晶的聚异丁烯PSA(DUKO-TAK-6908)较丙烯酸酯PSA透皮速率快且25 h累计透皮量大。含有-COOH官能团的PSA会与药物的仲胺基团作用,增加药物在PSA中的溶解度,减慢药物的透皮速率;与不添加任何促渗剂的空白基质相比,5种促渗剂均有不同程度的促渗效果,尤其是Transcutol对药物的促渗作用在5种促渗剂中效果最明显,与预测结果一致。结论通过药物的理化性质、药物在PSA中的溶解度及PSA官能团可以预测PSA对药物透皮性能的影响;对于在角质层中浓度低的药物,通过模型预测促渗剂对药物在角质层溶解度的影响,可以预测促渗剂的促渗效果,在此基础上进行处方筛选,可提高筛选效率。Objective To determine the effect of various pressure sensitive adhesives （PSA）, various functional groups of PSA and different permeation enhancers on the transdermal performance of tulobuterol. Methods Solubility of tulobuterol in the PSA was measured by observing drug crystallization in the patches containing different levels of tulobuterol raw material drug （API）. The effect of PSA on the transdermal performance of API was investigated by in-vitro permeation method with Franz diffusion cell system. In addition, the effects of lsopropyl myristate （IPM）, diethylene glycol monoethyl ether （Transcutol P）, glyceryl monolinoleate, azone, and diisopropyl adipate were predicted and proved by in vitro study with saturated paroline solution. Results The solubility of API in acrylic adhesive was much larger than that of polyisobutene PSA （DUKO-TAK-6908） and silicone PSA （BIO-4302）. The polyisobutene PSA （DUKO-TAK-6908） containing crystals provided a higher permeation rate and cumulative permeation amount at 25 hours than acrylic PSA. Due to interaction between PSA and the secondary amine groups of API, the solubility of tulobuterol in acrylic PSA with carboxyl group was increased, and the permeation rate was reduced. Transcutol P showed the highest permeation rate than other enhancers tested, consistent with the prediction. Conclusion Effect of PSA on the percutaneous absorption can be predicted by the physical and chemical properties of API, and the API solubility in the PSA and the functional groups of PSA. For API with has low solubility in the stratum corneum, we can first predict the effect of enhancers on the solubility of API in the stratum corneum, then choose enhancers which can improve the drug solubility in the stratum corneum in the next formulation screening.

关 键 词：妥洛特罗 压敏胶 透皮促渗剂 角质层溶解度 透皮性能 

分 类 号：R94[医药卫生—药剂学] TQ436[医药卫生—药学]