3-正丁基苯酞静脉注射亚微乳的制备和稳定性考察

目的制备3-正丁基苯酞(NBP)静脉注射亚微乳并考察其稳定性。方法采用高速剪切法制备初乳,二次高压均质法制备终乳。以灭菌前后乳剂的外观性状、粒径变化和稳定性常数(Ke)等为评价指标,考察制剂工艺的影响因素,同时采用正交设计实验优化处方。所得制剂分别在4、25、40℃条件下放置3个月,观察其外观性状、粒径、Zeta电位、pH值、药物含量、游离脂肪酸值和过氧化值等的变化。结果在优化处方及工艺条件下,所制备的NBP亚微乳稳定性良好,平均粒径为(128.0±3.4)nm(n=3),Zeta电位为-(34.3±5.3)mV(n=3)。稳定性实验结果表明,样品放置3个月后pH值降低约0.3,40℃条件下样品略变黄,其余各项指标无明显变化。结论该处方和工艺可行,制备的NBP亚微乳性质稳定,可供静脉使用。

Preparation and stability of 3-n-butylphthalide submicron emulsion for intravenous administration

Objective To prepare 3-n-butylphthalide (NBP) submicron emulsion for intravenous administration and investigate the stability. Methods The coarse emulsion which was obtained by high-shear mixing was homogenized into a fine monodispersed emulsion with a two-stage pressure homogenizer. The physical stability of emulsions was evaluated by the stability parameters of centrifugation, the appearance and the size change of the emulsions before and after sterilization. Processing parameters were studied and optimized.,and then the optimized formulation was selected through orthogonal experimental design. The selected NBP submicron emulsion was placed under the condition of 4, 25, 40℃ respectively. The appearance, size, zeta potential, pH, content of NBP, free fatty acid value and peroxidation value were investigated. Results A fine and stable NBP submicron emulsion was acquired under good processing control. The average particle size was 128.0±3.4nm（n=3） and the zeta potential was -34.3±5.3mv（n=3）. The colour of the NBP submicron emulsion under 40℃ was light yellow. The pH values under all temperature were decreased about 0.3 and the other values were almost the same. Conclusions The NBP submicron emulsion made by this optimum formulation and preparative technique was fitted to be used for intravenous administration.