Department of Pharmaceutics, The School of Pharmacy, University of London, 29-39 Brunswick Square, London WC1N 1AX, United Kingdom.
Int J Pharm. 2011 Apr 4;407(1-2):72-7. doi: 10.1016/j.ijpharm.2011.01.025. Epub 2011 Jan 21.
The aim of the present study was to investigate the permeation of fentanyl from supersaturated formulations when applied to silicone membrane. Silicone was chosen in order to separate the effects of supersaturation from other possible influences of volatile formulation components on biological membranes. Supersaturated formulations containing either propylene glycol/water (PG/H(2)O) or propylene glycol/ethanol (PG/Et) were prepared containing varying degrees of saturation (DS) of fentanyl. Permeation of finite and infinite doses of the PG/H(2)O formulations, and finite doses of the PG/Et formulations was investigated using Franz-type diffusion cells. For the PG/H(2)O formulations a good correlation between the flux and the DS of the formulation up to 5 DS for infinite dose studies (r(2)=0.99), and up to 7 DS for finite dose studies (r(2)=0.98), was evident. Similarly, for the PG/Et formulations there is a good correlation between the mean flux and the theoretical DS of the formulation (r(2)=0.95). Except for the 2 DS formulations, no significant differences were seen in the mean flux between PG/H(2)O and PG/Et finite dose studies. The larger fluxes observed for infinite doses of the PG/H(2)O formulations versus finite doses reflect changes in the effective area of diffusion over the time of the experiment for the latter set of experiments. The permeation enhancement observed for PG/Et formulations confirms that enhanced drug thermodynamic activity was induced by ethanol evaporation.
本研究旨在考察芬太尼从超饱和制剂向硅橡胶膜渗透的情况。之所以选择硅橡胶，是为了将超饱和状态对药物渗透的影响与挥发性制剂成分对生物膜的其他可能影响区分开来。本研究分别采用丙二醇/水（PG/H2O）和丙二醇/乙醇（PG/Et）作为溶剂，配制不同程度超饱和度的芬太尼制剂。采用 Franz 扩散池，对 PG/H2O 制剂的有限和无限剂量渗透情况，以及 PG/Et 制剂的有限剂量渗透情况进行了考察。对于 PG/H2O 制剂，无限剂量研究中，制剂的通量与超饱和度之间具有良好的相关性（r2=0.99），可达 5 倍超饱和度；有限剂量研究中，也具有良好的相关性（r2=0.98），可达 7 倍超饱和度。对于 PG/Et 制剂，同样也具有良好的相关性（r2=0.95）。除了 2 倍超饱和度制剂以外，PG/H2O 和 PG/Et 有限剂量研究中，平均通量之间并无显著差异。与有限剂量研究相比，无限剂量研究中 PG/H2O 制剂的通量更大，这反映了在后一组实验中，扩散有效面积随实验时间发生了变化。PG/Et 制剂中观察到的渗透增强证实，乙醇蒸发诱导了药物热力学活性的增强。
