奈多洛尔和香芹酮对尼可地尔经大鼠表皮膜体外渗透的影响。

Effect of nerodilol and carvone on in vitro permeation of nicorandil across rat epidermal membrane.

作者信息

Krishnaiah Yellela S R, Al-Saidan Saleh M, Chandrasekhar Dantam V, Rama Bukka

机构信息

Department of Pharmaceutics, Faculty of Pharmacy, Kuwait University, Kuwait.

出版信息

Drug Dev Ind Pharm. 2006 Apr;32(4):423-35. doi: 10.1080/03639040500528939.

DOI:10.1080/03639040500528939

PMID:16638680

Abstract

The objective of the study was to investigate the effect of nerodilol and carvone on the in vitro transdermal delivery of nicorandil so as to fabricate a membrane-moderated transdermal therapeutic system. The in vitro permeation studies were carried across the rat epidermal membrane from the hydroxypropyl methylcellulose (HPMC) gels (prepared with 70:30 v/v ethanol-water) containing selected concentrations of a terpene such as nerodilol (0%w/w, 4%w/w, 8%w/w, 10%w/w, or 12%w/w) or carvone (0%w/w, 4%w/w, 8%w/w, 12%w/w, or 16%w/w). The amount of nicorandil permeated (Q(24)) from HPMC gel drug reservoir without a terpene was 3424.6+/-51.4 microg/cm(2), and the corresponding flux of the drug was 145.5+/-2.2 microg/cm(2). h. The flux of nicorandil increased with an increase in terpene concentration in HPMC gel. It was increased ranging from 254.9+/-3.1 to 375.7+/-3.2 microg/cm(2).h or 207.6+/-4.7 to 356.7+/-15.3 microg/cm(2). h from HPMC gels containing nerodilol (4%w/w to 12%w/w) or carvone (4%w/w to 16%w/w), respectively. Nerodilol increased the flux of nicorandil by about 2.62-folds whereas carvone increased the flux of the drug by about 2.49-folds across the rat epidermal membrane. The results of the Fourier Transform Infrared (FT-IR) study indicated that the enhanced in vitro transdermal delivery of nicorandil might be due to the partial extraction of stratum corneum lipids by nerodilol or carvone. It was concluded that the terpenes, nerodilol and carvone, produced a marked penetration enhancing effect on the transdermal delivery of nicorandil that could be used in the fabrication of membrane-moderated transdermal therapeutic systems.

摘要

本研究的目的是研究奈多洛尔和香芹酮对尼可地尔体外透皮给药的影响，以便制备一种膜调节透皮治疗系统。体外渗透研究是通过大鼠表皮膜进行的，该表皮膜来自含有选定浓度萜烯（如奈多洛尔，0%w/w、4%w/w、8%w/w、10%w/w或12%w/w；或香芹酮，0%w/w、4%w/w、8%w/w、12%w/w或16%w/w）的羟丙基甲基纤维素（HPMC）凝胶（用70:30 v/v乙醇-水制备）。不含萜烯的HPMC凝胶药物储库中尼可地尔的渗透量（Q(24)）为3424.6±51.4μg/cm(2)，相应的药物通量为145.5±2.2μg/cm(2)·h。尼可地尔的通量随HPMC凝胶中萜烯浓度的增加而增加。含奈多洛尔（4%w/w至12%w/w）或香芹酮（4%w/w至16%w/w）的HPMC凝胶中，通量分别从254.9±3.1至375.7±3.2μg/cm(2)·h或207.6±4.7至356.7±15.3μg/cm(2)·h增加。奈多洛尔使尼可地尔的通量增加约2.62倍，而香芹酮使药物通量在大鼠表皮膜上增加约2.49倍。傅里叶变换红外（FT-IR）研究结果表明，尼可地尔体外透皮给药增强可能是由于奈多洛尔或香芹酮对角质层脂质的部分提取。得出的结论是，萜烯奈多洛尔和香芹酮对尼可地尔的透皮给药产生了显著的渗透增强作用，可用于制备膜调节透皮治疗系统。