Transdermal permeation of drugs with differing lipophilicity: Effect of penetration enhancer camphor

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• 作者：Feng Xie^a ; ^b ; Jia-ke Chai^a ; ^{chaijiake@sina.com" class="auth_mail" title="E-mail the corresponding author} ; Quan Hu^a ; Yong-hui Yu^a ; Li Ma^a ; Ling-ying Liu^a ; Xu-long Zhang^a ; Bai-ling Li^a ; Dong-hai Zhang^a
• 关键词：Camphor ; Penetration enhancer ; Transdermal permeation ; Microdialysis ; ATR-FTIR
• 刊名：International Journal of Pharmaceutics
• 出版年：2016
• 出版时间：30 June 2016
• 年：2016
• 卷：507
• 期：1-2
• 页码：90-101
• 全文大小：1993 K

文摘

The aim of the present study was to investigate the potential application of (+)-camphor as a penetration enhancer for the transdermal delivery of drugs with differing lipophilicity. The skin irritation of camphor was evaluated by in vitro cytotoxicity assays and in vivo transdermal water loss (TEWL) measurements. A series of model drugs with a wide span of lipophilicity (log P value ranging from 3.80 to −0.95), namely indometacin, lidocaine, aspirin, antipyrine, tegafur and 5-fluorouracil, were tested using in vitro transdermal permeation experiments to assess the penetration-enhancing profile of camphor. Meanwhile, the in vivo skin microdialysis was carried out to further investigate the enhancing effect of camphor on the lipophilic and hydrophilic model drugs (i.e. lidocaine and tegafur). SC (stratum corneum)/vehicle partition coefficient and Fourier transform infrared spectroscopy (FTIR) were performed to probe the regulation action of camphor in the skin permeability barrier. It was found that camphor produced a relatively low skin irritation, compared with the frequently-used and standard penetration enhancer laurocapram. In vitro skin permeation studies showed that camphor could significantly facilitate the transdermal absorption of model drugs with differing lipophilicity, and the penetration-enhancing activities were in a parabola curve going downwards with the drug log P values, which displayed the optimal penetration-enhancing efficiency for the weak lipophilic or hydrophilic drugs (an estimated log P value of 0). In vivo skin microdialysis showed that camphor had a similar penetration behavior on transdermal absorption of model drugs. Meanwhile, the partition of lipophilic drugs into SC was increased after treatment with camphor, and camphor also produced a shift of CH₂ vibration of SC lipid to higher wavenumbers and decreased the peak area of the CH₂ vibration, probably resulting in the alteration of the skin permeability barrier. This suggests that camphor might be a safe and effective penetration enhancer for transdermal drug delivery.