薄荷醇酯衍生物对压敏胶分散型贴剂中非甾体抗炎药体外经皮渗透性的影响

Influence of O-Acylmenthol Derivatives on in vitro Permeation of Nonsteroidal Antiinflammatory Drugs in Drug-in-adhesive Patches

制备了含不同非甾体抗炎药(酮洛芬、吲哚美辛和双氯芬酸)及促透剂[月桂氮酮、薄荷醇、庚酸薄荷醇酯(M-HEP)或油酸薄荷醇酯(M-OA)]的压敏胶分散型贴剂。采用双室扩散池,以离体大鼠皮肤为屏障进行体外渗透试验,考察了压敏胶和促透剂的种类对贴剂中药物渗透行为的影响。结果表明,用Duro-TAK 87-4098型压敏胶制备的贴剂中酮洛芬的稳态渗透速率和24 h累积透过量显著高于用其他两种压敏胶(Duro-TAK 87-2677和87-2852)制备的贴剂。各促透剂对酮洛芬促渗透作用依序为:M-HEP>M-OA>薄荷醇>月桂氮酮;对吲哚美辛的促渗透作用依序为:M-HEP>M-OA>月桂氮酮≈薄荷醇;M-OA和月桂氮酮对双氯芬酸有显著的促渗透效果,前者的促渗效果较强,而薄荷醇及M-HEP无促渗透作用。

The drug-in-adhesive patches loaded with ketoprofen, indometacin or diclofenac acid with different penetration enhancers [azone, menthol 2-isopropy-5-methylcyclohexyl heptanoate （M-HEP） or （E）-2-isopropyl-5- methylcyclohexyl octadec-9-enoate （M-OA） were prepared, respectively. The in vitro permeability test was carried out with two-chamber cell and excised rat skin to investigate the effects of the types of pressure sensitive adhesive （PSA） and penetration enhancer on permeation behavior of drug in patches. The results showed that the steady state permeation rate and cumulative amount at 24 h of ketoprofen in patches with Duro-TAK 87-4098 PSA were significantly higher than those of other patches with Duro-TAK 87-2677 or 87-2852 PSA. The effects of different penetration enhancers on ketoprofen were in the following order of M-HEP〉M-OA〉menthol〉azone and on indometacin were M-HEP〉M-OA〉azoneg menthol. M-OA and azone had significant effect on diclofenac acid （the former had a stronger effect）, while menthol and M-HEP had no enhancing effect.