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酮咯酸的经皮给药

Transdermal delivery of ketorolac.

作者信息

Amrish Chandra, Kumar Sharma Pramod

机构信息

Institute of Pharmacy, Bundelkhand University, Jhansi, India.

出版信息

Yakugaku Zasshi. 2009 Mar;129(3):373-9. doi: 10.1248/yakushi.129.373.

Abstract

A reservoir type transdermal patch for delivery of ketorolac, a potent analgesic agent was studied. The low permeability of skin is the rate-limiting step for delivery of most of the drugs. Studies were carried out to investigate the effect of permeation enhancers on the in vitro permeation of ketorolac across rat skin. The reservoir type transdermal patch was fabricated and the core was filled with gel system of a non ionic polymer HPMC (hydroxypropyl methyl cellulose) formulated in PBS (phosphate buffer saline) solution of pH of 5.4 along with isopropyl alcohol at 25% w/w concentration. Various permeation enhancers' viz. dimethyl sulphoxide, d-limonene, eucalyptus oil and transcutol (diethylene glycol monoethyl ether) were incorporated into the gel system. Permeation enhancement of ketorolac with different enhancers followed the order eucalyptus oil> transcutol> DMSO> d-limonene. Cyclic terpene containing eucalyptus oil was found to be the most promising chemical permeation enhancer for transdermal delivery of ketorolac. The increase in concentration of eucalyptus oil further enhanced drug permeation with maximum flux being achieved at 10% w/w of 66.38 microg/cm(2)/h. Further enhancement of permeation rate of ketorolac across skin was attained by application of abrading gel containing crushed apricot seed onto the skin. There was 5.16 times enhancement and flux of 93.10 microg/cm(2)/h was attained. A reservoir type transdermal patch for delivery of ketorolac thus appears to be feasible of delivering ketorolac across skin.

摘要

对一种用于递送强效镇痛剂酮咯酸的储库型透皮贴剂进行了研究。皮肤的低渗透性是大多数药物递送的限速步骤。开展了多项研究以考察渗透促进剂对酮咯酸经大鼠皮肤体外渗透的影响。制备了储库型透皮贴剂,其核心填充有由非离子聚合物羟丙基甲基纤维素(HPMC)在pH为5.4的磷酸盐缓冲盐水(PBS)溶液中配制而成的凝胶体系,并含有浓度为25%(w/w)的异丙醇。将各种渗透促进剂,即二甲亚砜、d-苎烯、桉叶油和透皮醇(二甘醇单乙醚)加入到凝胶体系中。不同促进剂对酮咯酸的渗透促进作用顺序为:桉叶油>透皮醇>二甲亚砜>d-苎烯。发现含环状萜烯的桉叶油是酮咯酸透皮递送最有前景的化学渗透促进剂。桉叶油浓度的增加进一步增强了药物渗透,在10%(w/w)时达到最大通量66.38μg/cm²/h。通过在皮肤上涂抹含有碾碎杏仁籽的研磨凝胶,可进一步提高酮咯酸经皮肤的渗透速率。通量提高了5.16倍,达到93.10μg/cm²/h。因此,一种用于递送酮咯酸的储库型透皮贴剂似乎能够实现酮咯酸经皮肤的递送。

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