氟非尼酮凝胶的研制及其体外透皮转运

Preparation and in vitro Transdermal Permeation of Fluorofenidone Gels

采用HPLC法测定了25℃、100 r/min条件下平衡48 h时氟非尼酮在水性溶剂和非水溶剂中的溶解度。结果表明,氟非尼酮在水及其他水性溶剂中微溶,溶解度约为2.5 mg/ml,溶剂的pH值对溶解度影响小;氟非尼酮易溶于乙醇,可溶于聚乙二醇400、1,2-丙二醇和异丙醇,微溶于甘油。摇瓶法测得氟非尼酮的油水分配系数(logP)值为1.182,略有亲脂性。以乳猪皮肤为模型,采用改良的Franz扩散池法评价不同载药量(0.5%和1%)凝胶及溶液的经皮渗透特性。结果表明,2种载药量的氟非尼酮凝胶的经皮渗透行为均符合零级模型,1%凝胶的24 h单位面积累积渗透量(Q24h)和单位面积皮肤滞留量(Qskin)均比0.5%凝胶增加约1倍;同时,0.5%溶液的Q24h和Qskin结果介于2种载药量凝胶之间。

The equilibrium solubilities of fluorofenidone in various aqueous and non-aqueous solvents after shaking at 25℃and 100 r/min for 48 h were determined by HPLC method.The results showed that fluorofenidone was slightly soluble in water and other aqueous solvents with the solubility about 2.5 mg/ml,and pH value of the aqueous solvents had little effect on its solubility.While in non-aqueous solvents,fluorofenidone was easily soluble in ethanol,soluble in polyethylene glycol(PEG) 400,1,2-propylene glycol and isopropanol,and slightly soluble in glycerin.The oil-water partition coefficient(logP) measured by the shake-flask method was 1.182.The transdermal permeation profiles of fluorofenidone from its solution and gels with drug loading of 0.5% and 1 % were evaluated by the modified Franz diffusion cell method with excised suckling pig skin as the barrier.The transdermal permeation behaviors of fluorofenidone from both gels were fitted to the zero-order model.And the cumulative permeation amount and the retention amount per unit area at 24 h(Q24 h,and Qskin) of the 1 % gels were both increased about twofold,compared with those of 0.5% gels.Meanwhile,the calculated values of Q24 h and Qskin for the solution were between those of the two gels.