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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。
OBJECTIVE To study the effects of aqueous phase pH, oleic acid, Tween-80 and other factors on the entrapment efficiency, drug-encapsulation efficiency of soybean oil as carrier and the basic components of milk droplets and soybean phospholipid as emulsifier. Particle size stability, and investigate the drug release behavior. Methods The crude milk was prepared by high-speed shear method. Phosphoric acid was used to adjust the pH value of the external aqueous phase of crude milk. The submicron milk was prepared by high pressure homogenization and the product was sterilized by high temperature and pressure. The particle size of the emulsion was measured by laser light scattering method. The pH of the emulsion was measured by acidometer. The changes of particle size, zeta potential and emulsion pH were observed after two storage periods. The high-speed and high-speed centrifugal separation of oil-water two-phase, high performance liquid chromatography-ultraviolet spectrophotometry determination of the aqueous phase and whole milk drug content and encapsulation efficiency, positive osmotic membrane dialysis assay emulsion chlorambucil in pH7.4 Phosphate buffered saline and the release curve was fitted. Results The lower the pH of the crude milk, the higher the entrapment efficiency of sodium chlorambucil in the final emulsion droplets. Oleic acid and Tween-80 contributed to the increase of entrapment efficiency and absolute zeta potential. The resulting emulsion showed a decrease in pH after 30 and 60 days of storage. Oleic acid prevented the increase of particle size and the absolute value of zeta potential, but Tween-80 did not have this effect. The drug has a pronounced burst phase, a slow release phase after the burst phase, the lower the encapsulation efficiency the higher the burst rate. Drug release consistent with Freundlich equation. Conclusions Adjusting the proper pH and choosing proper co-emulsifier can help to get the chlorambucil sodium emulsion with higher encapsulation efficiency, better stability and specific release behavior.