Escribano Elvira, Calpena Ana Cristina, Queralt Josep, Obach Rossend, Doménech Jose
Unitat de Biofarmàcia i Farmacocinética, Divisió IV, Facultat de Farmàcia, Universitat de Barcelona, c/Joan XXIII s/n, 08028 Barcelona, Spain.
Eur J Pharm Sci. 2003 Jul;19(4):203-10. doi: 10.1016/s0928-0987(03)00103-9.
The aim of this study was to improve the transdermal permeation of sodium diclofenac. Permeation studies were carried out in vitro using human skin (0.4 mm thick) from plastic surgery as a membrane. Four liquid formulations of 1% (w/w) sodium diclofenac were assayed: three ternary solvent systems (M4, M5, M6) and one microemulsion (M3). A 1% (w/w) solution of sodium diclofenac and a commercially available semisolid preparation were tested as reference formulations. The following permeation parameters for diclofenac were assessed: permeability coefficient, flux and drug permeated and retained in the skin at 24 h. The highest values of these parameters were obtained with formula M4, which contains transcutol 59.2%, oleic acid 14.9% and d-limonene 5% (w/w) as permeation enhancers. The anti-inflammatory activity of this formula was compared with that of the semisolid preparation on carrageenan-induced paw edema in rats. As expected from in vitro results, the M4 diclofenac delivery system showed higher activity than the semisolid preparation, both when applied locally (to the inflammation area) and when applied systemically (to the back). Neither treatment irritated the skin when tested on rabbits in a 72-h trial. These results suggest that topical delivery of sodium diclofenac with an absorption enhancer such as a mixture of oleic acid and d-limonene (M4) may be an effective medication for both dermal and subdermal injuries.
本研究的目的是提高双氯芬酸钠的透皮渗透率。使用整形手术获取的人皮肤(0.4毫米厚)作为膜进行体外渗透研究。测定了四种1%(w/w)双氯芬酸钠的液体制剂:三种三元溶剂体系(M4、M5、M6)和一种微乳剂(M3)。将1%(w/w)双氯芬酸钠溶液和一种市售半固体制剂作为参比制剂进行测试。评估了双氯芬酸的以下渗透参数:渗透系数、通量以及24小时时药物在皮肤中的渗透量和滞留量。这些参数的最高值是在含有59.2%的透皮醇、14.9%的油酸和5%(w/w)的d-柠檬烯作为渗透促进剂的M4配方中获得的。将该配方的抗炎活性与半固体制剂在角叉菜胶诱导的大鼠爪肿胀模型上的抗炎活性进行了比较。正如体外结果所预期的那样,M4双氯芬酸给药系统在局部应用(于炎症部位)和全身应用(于背部)时均显示出比半固体制剂更高的活性。在兔子身上进行的72小时试验中,两种治疗均未引起皮肤刺激。这些结果表明,使用油酸和d-柠檬烯混合物(M4)等吸收促进剂进行双氯芬酸钠的局部给药可能是治疗皮肤和皮下损伤的有效药物。