Department of Pharmaceutical Sciences Pietro Pratesi, Università degli Studi di Milano, Milan, Italy.
Int J Pharm. 2010 Feb 15;386(1-2):71-6. doi: 10.1016/j.ijpharm.2009.10.053. Epub 2009 Nov 10.
The in vitro passive diffusion of S-ibuprofen (S-IB) and RS-ibuprofen (RS-IB) through human epidermis was determined to study the effects of drug chirality. S-IB has a lower melting point (T(m)=54 degrees C) than RS-IB (T(m)=77 degrees C) and, therefore, a greater solubility (S-IB: 127+/-1 microg/mL; RS-IB: 81+/-1 microg/mL). Supersaturated plasters were prepared by using a poly(dimethylsiloxane) adhesive and Eugragit RL and propylene glycol as antinucleant agents. The in vitro skin permeation profiles were determined by Franz cells and human epidermis obtained from three different donors. The permeation profiles of S-IB from saturated solutions resulted statistically higher than those of RS-IB (p<0.002). When plasters were used, no differences were noticeable between the enantiomer and racemate (p>0.17). The latter unexpected results could be explained considering that the RS-IB or S-IB in vitro release rate constants, determined using 3% w/w or 6% w/w loaded plasters, were not statistically different, suggesting that the drug diffusivity within the adhesive matrix represented the rate limiting step to the skin absorption.
我们测定了 S-布洛芬（S-IB）和 R/S-布洛芬（RS-IB）在人体表皮中的体外被动扩散情况，以研究药物手性的影响。S-IB 的熔点（T(m)=54°C）比 RS-IB 低（T(m)=77°C），因此溶解度更大（S-IB：127+/-1μg/mL；RS-IB：81+/-1μg/mL）。我们采用聚二甲基硅氧烷（polydimethylsiloxane）粘合剂、Eugragit RL 和丙二醇作为抗结晶剂来制备超饱和贴剂。我们通过 Franz 细胞和来自三位不同供体的人体表皮来测定体外皮肤渗透情况。结果表明，S-IB 饱和溶液的渗透情况在统计学上显著高于 RS-IB（p<0.002）。而使用贴剂时，对映异构体和外消旋体之间没有明显差异（p>0.17）。考虑到使用 3% w/w 或 6% w/w 载药量贴剂测定的 RS-IB 或 S-IB 的体外释放速率常数并无统计学差异，我们可以解释出现这一意外结果的原因，即药物在粘合剂基质中的扩散率是皮肤吸收的限速步骤。
