Percutaneous Absorption of Salicylic Acid after Administration of Trolamine Salicylate Cream in Rats with Transcutol? and Eucalyptus Oil Pre-treated Skin

摘要

Purpose: This study was conducted to assess the effect of skin pre-treatment with Transcutol.and eucalyptus oil on systemic absorption of topical trolamine salicylate in rat. Methods:Pharmacokinetic parameters of salicylic acid following administration of trolamine salicylate on rat skin pre-treated with either Transcutol.or eucalyptus oil were determined using both non-compartmental and non-linear mixed effect modeling app roaches and compared with those of control group. Results: Median (% of interquartile range/median) of salicylic acid AUC0-8hr(ng/mL/hr) values in Transcutol. oreucalyptus oil treated rats were 2522(139%) and 58976(141%), respectivelyas compared to the 3023(327%)of the control group. Skin pre-treatment with eucalyptus oil could significantly decrease extravascular volume of distribution (V/F) and elimination rate constant (k) of salicylic acid. Conclusion: Unlike Transcutol., eucalyptus oil lead to enhanced transdermal absorption of trolamine salicylate through rat skin. var currentpos,timer; function initialize() { timer=setInterval("scrollwindow()",10);} function sc(){clearInterval(timer); }function scrollwindow() { currentpos=document.body.scrollTop; window.scroll(0,++currentpos); if (currentpos != document.body.scrollTop) sc();} document.onmousedown=scdocument.ondblclick=initialize296 | Sajjadi et al.Advanced Pharmaceutical Bulletin,2013, 3(2), 295-301Copyright . 2013 by Tabriz University of Medical SciencesMaterials and Methods Chemicals Trolamine salicylate, potassium dihydrogen phosphate, perchloric acid and acetonitrile ( HPLC-grade ) were purchased from Merck, Germany. Eucalyptus oil, containing 70% 1,8 ¨C cineole was from Barij Essence Company, Kashan, Iran . Transcutol.P (diethyleneglycol monoethyl ether) was kindly donated by Gattefosse, France. Animal Experiments and Drug Administration The study was approved by the ethics committee of the Vice Chancellor for Research and Technology of Ahvaz Jundishapur University of Medical Sciences. In vivo experiment was done on male wistar rats weighing 235 ?à 20 g which supplied by Animals Care and Breeding Center of Ahvaz Jundishapur University of Medical Sciences. Twelve hours before application of penetration enhancers (one day prior to dosing), the hair of the abdominal region was removed with electric hair clippers. The rats were divided into three groups. In pre-treated groups Transcutol. (N=10) or eucalyptus oil (N=5) in the form of closed dressing were applied to the hairless surface of abdominal skin for 12 hours. Subsequently, the closed dressing was removed and the pre-treated site was carefully wiped clean 50 times with cotton to remove the excess solution and then 1 gram of 10% trolamine salicylate(PERRIGO., USA) was applied to the pre-treated skin. In control group (N=7), trolamine salicylate was applied to the not-treated skin. Application area of depilated abdominal skin was 12 cm2 (3 ?á 4 cm). Rats were under sleep condition with 140 mg/kg intra-peritoneal phenobarbital during the period of pretreatment, application of drug and blood sampling. Blood samples were collected from a heparinized catheter inserted into the tail vein at 0.5, 1, 2, 4, 6, 8 and 10 hours (when it was possible) after administration of drug. Plasma samples were immediately separated by centrifugation at 13,000 rpm for 5 minutes and were stored at -70 ??C until the time of analysis. Analytical Procedure Salicylic acid concentration in rat plasma following topical administration of trolamine salicylate was determined using high-performance liquid chromatography (HPLC) with fluorescence detection as previously reported with some modifications.13The HPLC apparatus consisted of an Agilent 1260 Infinity quaternary pump and Agilent 1260 Infinity fluorescence detector (Agilent, USA ) . An Alltech Altima.C18 column (150 mm ?á 2.1 mm, 5 |ìm particle size) (Grace Davison Discovery Sciences, USA) was used for the separation. The mobile phase consisted of acetonitrile: phosphate buffer (17: 83) (pH 3) delivered at a flow rate of 0.5 ml/min. Fluorescence detection was performed at 297 nm (excitation) and 407 nm (emission). Plasma samples (50 |ìL) were transferred into a 1.5-ml micro-centrifuge tubes and mixed with 100 |ìL of perchloric acid 35%. After vo rtex mixing for 1 min, 300 |ìL of acetonitrile was added to this solution. The contents were vortex mixed thoroughly for 2 minutes and centrifuged at 1500 g for 5 minutes. Twenty |ìL of the clear supernatant was injected onto the column. Pharmacokinetic Analysis Non-Compartmental Analysis Area under the salicylic acid plasma concentration time curve between 0 and 8 hours post administration of trolamine salicylate (AUC0-8 hr) was calculated using trapezoidal rule to compare the extent of absorption in rats with Transcutol.or eucalyptus oil pre-treated skin with that of the control group. Kruskal -Wallis test followed by pairwise multiple comparisons (SPSS Statistics 20, IBM, USA) was used to check any significa