接受液中聚乙二醇400体积分数对药物体外透皮试验的影响
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摘要
目的:考察接受液中不同体积分数聚乙二醇(PEG) 400对药物体外透皮试验的影响。方法:选择5-氟尿嘧啶为模型药物,通过配制不同体积分数的PEG400磷酸盐缓冲液(PBS)作为接受液,接收室不加药,大鼠皮肤按正常操作条件处理12 h,后续用PBS置换出含PEG400的接受液,加药测定药物透皮吸收情况并计算相关透皮参数;采用扫描电镜观察离体大鼠皮肤在经含PEG400的接受液处理12 h后皮肤角质层形态变化。结果:体积分数为10%,15%和40%的PEG400-PBS组未影响相关药物透皮参数,体积分数为20%和30%的PEG400-PBS组的药物稳态透皮速率和累积透过量均明显高于PBS组(P <0. 01,P <0. 05);扫描电镜结果显示,当PEG400体积分数> 20%时,正常皮肤表面的褶皱逐渐消失,并伴有脱落的鳞片状物,同时30%PEG400-PBS组和40%PEG400-PBS组皮肤极度皱缩。结论:大鼠皮肤体外透皮试验中,接受液中PEG400用量应控制在20%以下。
Objective: To investigate the effect of varying concentrations of polyethylene glycol(PEG)400 in receiving solution on in vitro transdermal test of drugs. Method: 5-Fluorouracil(5-FU) was selected as a model drug,by preparing different concentrations of PEG400-phosphate buffer solution(PBS) as the receiving solution,the receiving chamber did not add drug,the excised rat skins were treated with various additives for12 h,then replaced by PBS and added the saturated model drug into the donor compartment to determine the transdermal parameters of the drug. Meanwhile,scanning electron microscopy(SEM) was employed to monitor the effect of PEG400 with different concentration on the stratum corneum of rat skin. Result: The 10%,15% and40% PEG400-PBS groups had no significant effect on in vitro transdermal absorption parameters of the 5-FU. The steady transdermal rate and cumulative penetration rate of the drug in 20% and 30% PEG400-PBS groups were significantly higher than that in the PBS group(P < 0. 01,P < 0. 05). SEM indicated that wrinkle of the intact rat skin gradually disappeared and a number of flakes were desquamated from the skin when the concentration of PEG400 was above 20% in receiving solution. Meanwhile,30% PEG400-PBS group and 40% PEG400-PBS group were extremely wrinkled. Conclusion: In the rat skin transdermal test,the concentration of PEG400 in receiving solution should be controlled below 20%.
Objective: To investigate the effect of varying concentrations of polyethylene glycol(PEG)400 in receiving solution on in vitro transdermal test of drugs. Method: 5-Fluorouracil(5-FU) was selected as a model drug,by preparing different concentrations of PEG400-phosphate buffer solution(PBS) as the receiving solution,the receiving chamber did not add drug,the excised rat skins were treated with various additives for12 h,then replaced by PBS and added the saturated model drug into the donor compartment to determine the transdermal parameters of the drug. Meanwhile,scanning electron microscopy(SEM) was employed to monitor the effect of PEG400 with different concentration on the stratum corneum of rat skin. Result: The 10%,15% and40% PEG400-PBS groups had no significant effect on in vitro transdermal absorption parameters of the 5-FU. The steady transdermal rate and cumulative penetration rate of the drug in 20% and 30% PEG400-PBS groups were significantly higher than that in the PBS group(P < 0. 01,P < 0. 05). SEM indicated that wrinkle of the intact rat skin gradually disappeared and a number of flakes were desquamated from the skin when the concentration of PEG400 was above 20% in receiving solution. Meanwhile,30% PEG400-PBS group and 40% PEG400-PBS group were extremely wrinkled. Conclusion: In the rat skin transdermal test,the concentration of PEG400 in receiving solution should be controlled below 20%.
引文
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[13] Costa P,Sousa-Lobo J M. Modeling and comparison of dissolution profiles[J]. Eur J Pharm Sci,2001,13(2):123-133.
[14]王艳宏,刘书博,王锐,等.中药挥发油促透皮吸收及透皮吸收作用的研究进展[J].中国实验方剂学杂志,2017,23(3):192-199.
[2]王艳宏,齐笑,关枫,等.马钱子总碱中2种成分的平衡溶解度、油水分配系数、体外透皮特性[J].中成药,2017,39(10):2034-2038.
[3]罗国平,闫梦茹,孟会宁,等.地肤子总皂苷凝胶剂的制备及体外透皮吸收实验研究[J].应用化工,2017,46(12):2420-2423.
[4] Bronaugh R L,Stewart R F. Methods for in vitro percutaneous absorption studiesⅢ:hydrophobic compounds[J]. J Pharm Sci,1984,73(9):1255-1258.
[5] Challapalli P V,Stinchcomb A L. In vitro experiment optimization for measuring tetrahydrocannabinol skin permeation[J]. Int J Pharm,2002,241(2):329-339.
[6] Moloney S J. The in vitro percutaneous absorption of glycerol trioleate through hairless mouse skin[J]. J Pharm Pharmacol,1988,40(11):819-821.
[7]霍仕霞,高莉,彭晓明,等.高良姜素的体外透皮吸收特性研究[J].中国药房,2017,28(19):2631-2634.
[8]李璐,周建明,杨一帆,等.复方南星止痛膏活性成分在不同接收介质中的透皮扩散行为比较[J].中国实验方剂学杂志,2018,24(3):1-7.
[9]兰颐,王琼,安静,等.不同接受液对药物体外透皮试验的影响[J].中国实验方剂学杂志,2013,19(13):7-10.
[10]张迪,郭宏伟,孙宽,等. HPLC法测定复方氟尿嘧啶注射液含量及有关物质[J].中国药师,2012,15(3):356-358.
[11] LI G F,Kaminyama F,LIU L J,et al. Influence of different layers of skin on the percutaneous absorption of drugs with different lipophilcity[J]. Mil Med Res,2002,17(2):152-156.
[12]卓如意,董伟,张旭,等.靶向硫酸庆大霉素的制备及体外抗菌试验[J].动物医学进展,2008,29(1):36-38,52.
[13] Costa P,Sousa-Lobo J M. Modeling and comparison of dissolution profiles[J]. Eur J Pharm Sci,2001,13(2):123-133.
[14]王艳宏,刘书博,王锐,等.中药挥发油促透皮吸收及透皮吸收作用的研究进展[J].中国实验方剂学杂志,2017,23(3):192-199.