白芷香豆素脂质体的制备及质量评价

Preparation and Quality Evaluation of Angelicae Dahuricae Radix Coumarin Liposomes

目的:优化白芷香豆素脂质体的处方工艺并考察其释药性能。方法:采用薄膜-超声法制备白芷香豆素脂质体,在单因素试验基础上,以包封率、载药量为综合评价指标,利用Box-Behnken响应面试验考察脂胆比、脂药比和超声时间对处方工艺的影响,利用紫外分光光度法测定白芷香豆素含量,透射电镜观察脂质体的粒径形态及大小。结果:白芷香豆素脂质体最佳处方工艺为脂胆比(6∶1);脂药比(5∶1),超声时间34 min;制备的脂质体粒径均匀,呈球形小囊泡,分散性好,粒径(112.08±1.21)nm,包封率(94.02±1.56)%,载药量(5.42±0.35)%;游离白芷香豆素3 h的累积释放率达100%,空白脂质体与白芷香豆素的混合溶液12 h累积释放率95.3%,白芷香豆素脂质体12 h累积释放率45.6%。结论:该处方工艺稳定可行,制备的白芷香豆素脂质体包封率较高,形态和粒径较均匀,具有明显的缓释效果。

Objective： To optimize formulation technology of Angelicae Dahuricae Radix coumarin liposomes and investigate its release properties. Method： Liposomes of coumarin from Angelicae dahuricae Radix were prepared by film dispersion-supersonic method, based on single factor tests, with encapsulation efficiency and drug loading as comprehensive evaluation index, Box-Behnken design-response surface method was adopted to optimize formulation technology with proportion of phosphatidylcholine to cholesterin, ratio of phosphatidyleholine to coumarin and ultrasonic time as factors. The content of coumarin was determined by UV spectrophotometry, appearances and particle size of coumarin liposomes were examined with transmission electron microscopy. Result： Optimum formulation technology was as following： proportion of phosphatidyleholine to eholesterin （6：1 ）, proportion of phosphatidylcholine to coumarin （5：1 ） , ultrasonic time 34 min; Prepared coumarin liposomes had uniform size, showed spherical vesicles with good dispersion, particle size was （112.08 ± 1.21 ） nm, encapsulation efficiency was （94.02-1.56） % , drug loading was （5, 42 ± 0.35 ） %. Cumulative release of eoumarin was 100% in 3 h, cumulative release of mixed solution of coumarin and blank liposomes was 95.3% within 12 h, but that of Angelicae dahuricae Radix coumarin liposomes was 45.6% in 12 h. Conclusion： This optimized process was stable and suitable for industrial production, prepared eoumarin liposomes had high encapsulation efficiency and significant release effects with uniform morphology and particle size.