甲氨蝶呤磷脂复合物的制备及体外透皮考察

Preparation and in vitro Transdermal Permeation of Methotrexate Phospholipid Complex

以甲氨蝶呤与磷脂的复合率为评价指标,采用单因素试验和正交设计优化复合物制备工艺。结果表明,优化的制备工艺为复合温度40℃,甲氨蝶呤浓度为30 mg/ml,药物:磷脂摩尔比1:2。以离体乳猪皮肤作渗透屏障,采用改良直立式Franz扩散池法进行体外透皮研究。结果表明,甲氨蝶呤磷脂复合物24 h累积渗透量低于游离药物,在表皮及真皮层的滞留量则分别是游离药物组的2.1和2.3倍。提示甲氩蝶呤磷脂复合物可增加药物皮肤滞留量,并减小经皮透过量。

The preparation of methotrexate phospholipid complex （1-PLC） was optimized by single factor test and orthogonal design with the binding ratio as index. The optimal conditions for 1-PLC were as follows： temperature was 40 ℃, concentration of I was 30 mg/ml, the ratio of 1 to phospholipid was 1 ： 2. The modified Franz diffusion cell was employed for the in vitro transdermal permeation test with the excised piglet skin as the barrier. The results showed that the cumulative penetration at 24 h of 1-PLC was lower than the free drug, but the cumulative amounts in both epidermal and dermal layer were 2.1 and 2.3 times higher than free drug. It indicated that MTX-PLC could enhance the skin retention and reduce the permeation of 1 simultaneously.