Department of Pharmaceutics, University of London, London, UK.
Int J Pharm. 2011 Sep 15;416(1):155-9. doi: 10.1016/j.ijpharm.2011.06.024. Epub 2011 Jun 23.
Supersaturation has previously been studied as a mechanism to enhance membrane transport of fentanyl from propylene glycol:water formulations (PG:H(2)O) across silicone. In this study these supersaturated fentanyl formulations were evaluated in human skin. A number of polymers were also screened for their ability to stabilise the supersaturated formulations and permeation was evaluated for both infinite and finite doses. For infinite dose studies, permeation in skin increased linearly with increasing degree of drug saturation (DS) for formulations containing 0.5, 1, 2 DS of fentanyl and a 3 DS formulation stabilised with 1% (w/v) hydroxypropylcellulose (HPC). An excellent correlation was obtained for flux values in silicone compared with flux values in skin, for infinite dose studies for formulations containing 0.5, 1, 2 DS of fentanyl and the 3 DS formulation stabilised HPC. The concentration of the fentanyl in the stratum corneum also increased in proportion to the DS. However the same trend was not observed for finite dose studies. This is because the depletion of the solvent carrier promotes drug crystallisation with consequent implications for membrane transport. Tape-stripping experiments indicated that supersaturation of the drug is maintained in the outer layers of the stratum corneum. The ideal vehicle must, therefore, maintain the drug in solution on and in the skin in a sustained manner for effective transdermal delivery.
先前已有研究表明，超饱和状态可增强芬太尼从丙二醇：水制剂（PG：H2O）穿过硅酮向人体皮肤中传递的作用。在本研究中，对这些超饱和芬太尼制剂在人体皮肤中的情况进行了评估。还筛选了许多聚合物以稳定超饱和制剂的能力，并对无限剂量和有限剂量条件下的渗透情况进行了评估。对于无限剂量研究，对于含有 0.5、1 和 2 个 DS 的芬太尼制剂和用 1%（w/v）羟丙基纤维素（HPC）稳定的 3 DS 制剂，渗透量随药物饱和度（DS）的增加而线性增加。在无限剂量研究中，对于含有 0.5、1 和 2 个 DS 的芬太尼制剂和用 HPC 稳定的 3 DS 制剂，在硅酮中的通量值与在皮肤中的通量值之间存在极好的相关性。在角层中的芬太尼浓度也与 DS 成正比增加。然而，对于有限剂量研究，并未观察到相同的趋势。这是因为溶剂载体的耗尽会促进药物结晶，从而对膜传输产生影响。胶带剥离实验表明，药物在角层的外层保持超饱和状态。因此，理想的载体必须以持续的方式将药物维持在溶液中并在皮肤中，以实现有效的经皮输送。
