卡维地洛经猪皮的体外渗透：载体和渗透促进剂的作用

In vitro permeation of carvedilol through porcine skin: effect of vehicles and penetration enhancers.

作者信息

Gannu Ramesh, Vishnu Y Vamshi, Kishan V, Rao Y Madhusudan

机构信息

Centre for Biopharmaceutics and Pharmacokinetics, University College of Pharmaceutical Sciences, Kakatiya University, Warangal-506 009 (A.P), India.

出版信息

PDA J Pharm Sci Technol. 2008 Jul-Aug;62(4):256-63.

PMID:19174954

Abstract

This investigation studied the effect of vehicles on the in vitro permeation of carvedilol from saturated solutions across porcine skin and selected appropriate penetration enhancers. Labrasol, Transcutol, polyethylene glycol 400, propylene glycol, ethanol, oleic acid, isopropyl myristate, and phosphate buffered saline (pH 7.4) containing 40% v/v polyethylene glycol 400 as control, were used as vehicles; limonene, carvone, camphor, menthol, Transcutol, and Labrasol at 5% w/v concentrations were used as penetration enhancers. Skin permeation studies were conducted in Franz diffusion cells using excised porcine ear skin. Solubility was highest (369.13 mg/mL) in Transcutol, whereas isopropyl myristate showed the lowest solubility (0.79 mg/mL) among all the vehicles. The flux of carvedilol from Transcutol, Labrasol, polyethylene glycol 400, ethanol, and oleic acid was 10.5, 8.6, 4.2, 2.9, and 1.5 times higher, respectively, than that observed with control. The flux obtained using Transcutol was significantly higher (P < 0.05) than the flux obtained using the other vehicles. However, the flux values of carvedilol using isopropyl myristate (P < 0.01) and propylene glycol (P < 0.05) were significantly lower than that of the control. Solutions containing 5% w/v camphor showed maximum permeation (232.54 microg) in 24 h with a flux of 3.19 microg/cm2/h, which was significantly different (P < 0.05) than the flux obtained using other permeation enhancers. The control sample showed lowest permeation (30.50 microg), with a flux of 0.33 microg/cm2/h. The flux of carvedilol from the solutions containing 5% w/v camphor, limonene, Transcutol, carvone, Labrasol, and menthol were 9.7, 7.6, 7.6, 6.3, 4.7, and 2.3 times higher, respectively, than that observed using the control. The present study suggests that Transcutol, Labrasol, and polyethylene glycol 400 may be used as potential vehicles and camphor, limonene, and Transcutol at a 5% w/v level as penetration enhancers.

摘要

本研究考察了不同溶媒对卡维地洛饱和溶液经猪皮体外渗透的影响，并筛选合适的渗透促进剂。以Labrasol、Transcutol、聚乙二醇400、丙二醇、乙醇、油酸、肉豆蔻酸异丙酯以及含40%（v/v）聚乙二醇400的磷酸盐缓冲液（pH 7.4）作为对照溶媒；以5%（w/v）浓度的柠檬烯、香芹酮、樟脑、薄荷醇、Transcutol和Labrasol作为渗透促进剂。采用Franz扩散池，以猪耳离体皮肤进行皮肤渗透研究。在所有溶媒中，卡维地洛在Transcutol中的溶解度最高（369.13 mg/mL），而在肉豆蔻酸异丙酯中的溶解度最低（0.79 mg/mL）。卡维地洛从Transcutol、Labrasol、聚乙二醇400、乙醇和油酸中的通量分别比对照高10.5、8.6、4.2、2.9和1.5倍。使用Transcutol获得的通量显著高于使用其他溶媒获得的通量（P < 0.05）。然而，使用肉豆蔻酸异丙酯（P < 0.01）和丙二醇（P < 0.05）时卡维地洛的通量显著低于对照。含5%（w/v）樟脑的溶液在24小时内显示出最大渗透量（232.54 μg），通量为3.19 μg/cm²/h，与使用其他渗透促进剂获得的通量相比有显著差异（P < 0.05）。对照样品的渗透量最低（30.50 μg），通量为0.33 μg/cm²/h。含5%（w/v）樟脑、柠檬烯、Transcutol、香芹酮、Labrasol和薄荷醇的溶液中卡维地洛的通量分别比对照高9.7、7.6、7.6、6.3、4.7和2.3倍。本研究表明，Transcutol、Labrasol和聚乙二醇400可作为潜在的溶媒，5%（w/v）浓度的樟脑、柠檬烯和Transcutol可作为渗透促进剂。