静脉注射用硝酸甘油亚微乳的制备工艺及其质量评价

Preparation and Evaluation of Nitroglycerin Submicron Emulsion for Intravenous Administration

优化制备静脉注射用硝酸甘油亚微乳,所得处方为硝酸甘油0.2%,大豆油10.0%,蛋黄磷脂1.8%,泊洛沙姆1.8%,油酸0.12%,甘油2.25%。油水相于70℃混合后,采用高速剪切乳化法于4000r/min乳化10min制备初乳,再高压均质(80MPa)15次得成品。所得乳剂平均粒径为156.4nm,ζ电位-39mV,pH7.1。其渗透压与稀释液(用5%葡萄糖注射液或生理盐水稀释10倍)的渗透压均接近等渗,提示乳剂与稀释液配伍相容性良好。初步考察表明乳剂在4℃下较稳定。

The optimized formulation for preparation of nitroglycerin submicron emulsion for intravenous administration was as follows：nitroglycerin 0.2%,soybean oil 10%,egg yolk lecithin 1.8%,Poloxamer 188 1.8%,oleic acid 0.12% and glycerine 2.25%.The water phase mixed with oil phase at 70 ℃,then crude emulsion was obtained by high speed shearing method for 10 min at 4 000 r/min.The submicron emulsion was prepared by the high pressure homogenization at 80 MPa for 15 times.The mean diameter of the products was 156.4 nm with ζ potential of-39 mV and pH value of 7.1.The osmotic pressure of nitroglycerin submicron emulsion and its diluted solutions（to one tenth concentration with 5% glucose injection or saline） were almost isosmotic.It indicated that the compatibility of submicron emulsion with the above two diluents was good.The results of preliminary stability test showed that nitroglycerin submicron emulsion was stable at 4 ℃.