维生素K_1自纳米乳化释药系统的质量控制及理化性质

Quality control and physico-chemical properties of vitamin K_1 self-nanoemulsifying drug delivery systems

目的建立维生素K1(VK1)自纳米乳化释药系统(VK1-SNEDDS)溶出度、含量及有关物质检测方法,并对制剂理化性质进行研究。方法采用紫外分光光度法测定VK1-SNEDDS的溶出度,高效液相色谱(HPLC)法测定VK1和有关物质含量,并考察SNEDDS的外观、形态、粒度、电位、自乳化速率。结果 VK1紫外分光光度法的线性范围是0.85~20.4μg/ml,其HPLC法的线性范围是2.16~216μg/ml,各自的回收率、精密度、专属性、灵敏度等均符合要求;稀释后SNEDDS能迅速形成澄清透明的纳米乳,透射电镜下乳滴呈圆球形,粒径均一,平均为47.74 nm,zeta电位为-20.53 m V。结论 VK1-SNEDDS的溶出度、含量及有关物质检测方法准确可靠,其加水稀释后形成均一稳定的纳米乳,可显著提高VK1溶出度。该检测方法准确可靠,可用于制剂的质量控制。

Objective To establish assay methods for the determination of dissolution,content and related substances of vitamin K1self-nanoemulsifying drug delivery system（VK1-SNEDDS）,and investigate the physico-chemical properties of the preparation.Methods The UV method was established to determine the dissolution of VK1-SNEDDS. The content and related substances were determined by HPLC. The appearance,self-emulsification time,micro-morphology,droplet size and zeta potential were also investigated. Results The linearity range of established UV and HPLC methods was 0.85-20.4 and 2.16-216 μg/ml,respectively,and all the recovery,precision,specificity and sensitivity met requirements. VK1-SNEDDS could disperse quickly after dilution. The transmission electron microscope（TEM）image of the optimized liquid SNEDDS showed that most of the emulsion droplets were of uniform size with no signs of coalescence. Droplet size of optimal formulation was revealed as 47.74 nm with polydispersibility index（PDI）of 0.248,and zeta potential was found to be-20.53 m V. Conclusion VK1-SNEDDS could form homogeneous and stable nanoemulsion when diluted with aqueous phase and increase the dissolution of lipophilic drug. The methods are reliable,accurate and suitable for quality control of VK1-SNEDDS.