苯丁酸氮芥脂质体的制备及处方因素考察

Preparation and Study on Formulation of Chlorambucil Liposome

关键词:  苯丁酸氮芥  脂质体  包封率  单因素  正交设计

Key words:  chlorambucil  liposome  encapsulation efficiency  single factor  orthogonal design

摘要:

目的 制备苯丁酸氮芥脂质体并优化其处方。方法 薄膜超声分散法制备苯丁酸氮芥脂质体，采用微柱离心-HPLC法测定其包封率，以包封率为考察指标，研究膜材比、药脂比、水相介质pH值以及磷脂浓度等因素对脂质体包封率的影响；通过正交试验对处方进行优化，并进行质量评价。结果 苯丁酸氮芥脂质体优化后的制备处方为胆固醇与磷脂质量比1∶3、药脂比1∶10、水相介质pH值为7.4、磷脂浓度为0.3%。按该处方制得的苯丁酸氮芥脂质体包封率>87%，平均粒径为84.71 nm，PDI为0.167。结论 优选处方稳定可行，制备的苯丁酸氮芥脂质体包封率高、粒径小且均匀。

Abstract:

OBJECTIVE To prepare chlorambucil liposome, and to optimize the formulation of chlorambucil liposome. METHODS Chlorambucil liposome were prepared by film-ultrasound method and the encapsulation efficiency was measured by microcolumn centrifugation-HPLC method. The single factors such as the ratio of cholesterol to phospholipid, the ratio of drug to phospholipid, the pH value of aqueous phase and the concentration of phospholipid were studied. And the orthogonal design was adopted to obtain the optimized prescription, and the quality evaluation was carried out. RESULTS The best prescription was as follows:the ratio of cholesterol to phospholipid was 1:3; the ratio of drug to phospholipid was 1:10; the pH value of aqueous phase was 7.4 and the concentration of phospholipid was 0.3%. The encapsulation efficiency of the chlorambucil liposome prepared according to the prescription was >87%, the average particle size was 84.71 nm, and the PDI was 0.167. CONCLUSION The chlorambucil liposome prepared according to the optimized formulation has higher encapsulation efficiency with small and uniform particle size.