苯丁酸氮芥钠亚微乳储存后的粒径变化及释药行为

发布时间：2018-02-19 18:19

本文关键词： 亚微乳苯丁酸氮芥钠高压均质法包封率稳定性 Freundlich方程　出处：《沈阳药科大学学报》2017年11期 　论文类型：期刊论文

【摘要】：目的以大豆油为药物载体及乳滴基本成分,大豆磷脂为乳化剂,制备苯丁酸氮芥钠亚微乳,考察水相pH,油酸,吐温-80等因素对药物包封率、粒径稳定性的影响,并考察药物的释放行为。方法采用高速剪切法制备粗乳,磷酸调节粗乳外水相pH值,高压均质法制备亚微乳,密封高温高压灭菌得最终产品。激光动态光散射法测定乳滴粒径,酸度计测定乳剂的pH,考察两个时间段的储存期后的乳滴粒径、ζ电位和乳剂pH的变化。低温高速离心分离油水两相,高效液相色谱-紫外分光光度法测定水相及全乳的药物含量并得到包封率,正渗透膜透析法考察乳剂中苯丁酸氮芥钠在pH7.4的磷酸缓冲盐中的释放行为并对释放曲线进行拟合。结果粗乳pH值越低,苯丁酸氮芥钠在最终产品乳滴中的包封率越高,油酸和Tween-80有助于包封率和ζ电位绝对值的提高。所得乳剂在储存30、60 d后,均出现pH降低的现象。油酸防止了粒径的增长和ζ电位绝对值的降低,Tween-80未有此作用。药物有明显的突释相,突释相过后呈现缓释相,包封率越低突释率越高。药物的释放符合Freundlich方程。结论调节合适的pH,选用合适的助乳化剂,有助于得到包封率较高、稳定性较好、呈现特定缓释行为的苯丁酸氮芥钠乳剂。
[Abstract]:Objective to study the effects of pH of aqueous phase, oleic acid and Tween-80 on encapsulation efficiency and particle size stability of nitromustard sodium phenylbutyrate, using soybean oil as drug carrier and milk droplet as basic component and soybean phospholipid as emulsifier. Methods crude emulsion was prepared by high speed shear method, pH value of external water phase was adjusted by phosphoric acid, sub-microemulsion was prepared by high pressure homogenization method, the final product was obtained by sealing high temperature and high pressure sterilization, and the particle size of emulsion was determined by laser dynamic light scattering method. The pH of emulsion was determined by acidometer, and the changes of particle size, 味 potential and pH of emulsion after storage period were investigated. The oil-water phase was separated by centrifugation at low temperature and high speed. High performance liquid chromatography-ultraviolet spectrophotometry was used to determine the drug content in aqueous phase and whole milk, and the encapsulation efficiency was obtained. The release behavior of nitrogen mustard phenylbutyrate in phosphate buffer salt of pH7.4 was investigated by normal permeation membrane dialysis and the release curve was fitted. Results the lower the pH value of crude emulsion, the higher the entrapment efficiency of nitrogen mustard phenylbutyrate sodium in the final product. Oleic acid and Tween-80 can increase the entrapment efficiency and the absolute value of 味 potential. Oleic acid prevented the increase of particle size and the decrease of the absolute value of 味 potential. Tween-80 had no such effect. The lower the encapsulation efficiency, the higher the sudden release rate. The drug release accords with the Freundlich equation. Conclusion adjusting the appropriate pH and selecting the appropriate co-emulsifier can help to obtain the sodium butyrate emulsion with higher entrapment efficiency and better stability, showing a specific slow-release behavior.
【作者单位】：锦州医科大学药学院;辽宁省药物作用与质量评价工程技术研究中心;锦州医科大学公共基础学院;
【基金】：国家自然科学基金资助项目(511021178) 辽宁省科技厅资助项目(2014022041) 中国博士后基金资助项目(2014M561187)
【分类号】：R943

【相似文献】