Lee Philip J, Ahmad Naina, Langer Robert, Mitragotri Samir, Prasad Shastri V
Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, USA.
Int J Pharm. 2006 Feb 3;308(1-2):33-9. doi: 10.1016/j.ijpharm.2005.10.027.
The effect of various classes of chemical enhancers was investigated for the transdermal delivery of the anesthetic lidocaine across pig and human skin in vitro. The lipid disrupting agents (LDA) oleic acid, oleyl alcohol, butenediol, and decanoic acid by themselves or in combination with isopropyl myristate (IPM) showed no significant flux enhancement. However, the binary system of IPM/n-methyl pyrrolidone (IPM/NMP) improved drug transport. At 2% lidocaine dose, this synergistic enhancement peaked at 25:75 (v/v) IPM:NMP with a steady state flux of 57.6 +/- 8.4 microg cm(-2) h(-1) through human skin. This observed flux corresponds to a four-fold enhancement over a 100% NMP solution and over 25-fold increase over 100% IPM at the same drug concentration (p < 0.001). NMP was also found to co-transport through human skin with lidocaine free base and improve enhancement due to LDA. These findings allow a more rational approach for designing oil-based formulations for the transdermal delivery of lidocaine free base and similar drugs.
研究了各类化学促进剂对麻醉剂利多卡因经猪皮和人皮体外透皮给药的影响。脂质破坏剂（LDA）油酸、油醇、丁二醇和癸酸单独使用或与肉豆蔻酸异丙酯（IPM）联合使用均未显示出显著的通量增强。然而，IPM/ N -甲基吡咯烷酮（IPM/ NMP）二元体系改善了药物转运。在利多卡因剂量为2%时，这种协同增强作用在IPM:NMP为25:75（v/v）时达到峰值，通过人皮的稳态通量为57.6±8.4 μg cm⁻² h⁻¹。在相同药物浓度下，观察到的通量比100% NMP溶液提高了四倍，比100% IPM提高了25倍以上（p < 0.001）。还发现NMP与利多卡因游离碱共同经人皮转运，并增强了LDA的促进作用。这些发现为设计用于利多卡因游离碱及类似药物透皮给药的油基制剂提供了更合理的方法。
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