HPLC测定吲哚美辛亚微乳胶含量及其体外经皮渗透评价

Determination of IMC-Submicron Emulsion Gel Content by HPLC and Evaluation of the Drug Transdermal Pemeation in Vitro

关键词:  吲哚美辛  亚微乳胶  体外经皮渗透  渗透系数

Key words:  indomethacin  submicron emulsion gel  transdermal permeation in vitro  permability rate

摘要:

目的建立测定吲哚美辛亚微乳胶含量的高效液相色谱法，并评价其在离体大鼠皮肤中的渗透性。方法采用Hypersil BDS C18柱(4.6 mm×200 mm，5 μm)；流动相为乙腈-水-冰乙酸(50∶50∶0.06)；流速1.0 mL·min-1，检测波长228 nm，柱温40 ℃，外标法定量计算结果。改良Franz扩散池测定药物在离体大鼠皮肤中的渗透量。结果吲哚美辛在8.46～126.90 μg·mL-1内线性关系良好(r=0.999 9)，平均回收率为99.60%，RSD为1.35%(n=9)。吲哚美辛亚微乳胶24 h平均累积透过量为(1 311.38±74.95) μg·cm-2，渗透系数为(54.17±4.91) μg·cm-2·h，渗透行为经拟合符合零级动力学过程。结论本试验建立的方法准确可靠、简单快速，适用于该制剂的含量测定及体外经皮特性研究。

Abstract:

OBJECTIVE To establish an HPLC method for determining the content of IMC-submicron emulsion gel and study the drug permeation in vitro rat skin. METHODS The HPLC system consisted of analytical column of Hypersil BDS C18 (4.6 mm×250 mm, 5 μm), mobile phase of a mixture of acetonitrile-water-acetic acid (50∶50∶0.06), the flow rate of mobile phase was 1.0 mL·min-1. UV detector was set at 228 nm, and the coloumn temperature was 40 ℃. It was determined by externalstandard method. The drug pemeation amount in vitro rat skin was detected by modified Franz diffusion cell. RESULTS The linearity between concentration and peak area ratio was obtained from 8.46-126.90 μg·mL-1 (r=0.999 9). The mean recovery of IMC were 99.60%, RSD was 0.20% (n=9). The average pemeation amount of IMC-submicron emulsion gel in 24 h was (1311.38±74.95) μg·cm-2, permability rate was (54.17±4.91) μg·cm-2·h, and the permeation behavior in vitro followed the zero-order kinetic equation. CONCLUSION The method built in this study is accurate and reliable, applicable to assay the content and to evaluate the transdermal character in vitro of this preparation.