卵磷脂/果胶锌复合凝胶球的制备及性能

采用滴制法, 以吲哚美辛(IDM)为模型药物, 皂化高甲氧化苹果果胶为骨架材料, 氯化锌为交联剂, 并复合卵磷脂(PC)制成吲哚美辛卵磷脂/果胶锌复合凝胶球。针对工艺参数对复合凝胶球粒径、粒重、载药量与包封率以及体外释药性能的影响进行了讨论。凝胶球均成均匀球形, 粒径1.13~1.42 mm, 粒重1.13~2.32 mg, 包封率范围70.72%~94.76%, 载药量范围5.84%~13.54%。同时实验结果表明, 卵磷脂的加入比例、药胶比(吲哚美辛与果胶的质量比)和皂化用NaOH浓度对复合凝胶球的形态、载药及释药性能均有明显影响。其中, 卵磷脂的加入使复合凝胶球载药性能和在模拟肠液中的缓释性能明显提高, 当卵磷脂与果胶的质量比为5:4, 皂化用NaOH浓度为30 g/L, 药胶质量比1:4时, 复合凝胶球在肠模拟液中8 h累计释药率为8.93%。稳定性实验结果表明, 在高温和光照的条件下放置, 卵磷脂/果胶锌复合凝胶球比原药及果胶锌凝胶球具有更好的稳定性, 显示出卵磷脂对果胶锌复合凝胶球在结肠定位给药系统的明显改善作用。

Preparation and properties of lecithin/zinc pectin composite microspheres

Lecithin/zinc-pectin composite microspheres were designed and developed as colon-specific carrier. The novel complex hydrogel microspheres were prepared from polymers: pectin, a carbohydrate from plants, and lecithin(PC), a phospholipid from soybean. Indomethacin (IDM) was chosen as model drug and sapond saponified high-methylated apple pectin as framework material. Intermolecular cross-links were formed between the negatively charged carboxyl groups and the positively charged zinc ions, and gel microspheres were produced. Effect of parameters on size, mass, encapsulation efficiency, drug loading, and drug release pattern of the microspheres were investigated. It is found that formulations were spherical with diameter of 1.13-1.42 mm, mass of 1.13-2.32 mg, encapsulation efficiency of 70.72%-94.76%, and drug loading of 5.84%-13.54%. It is also found that the morphology of microspheres and their loading/releasing capacity are significantly influenced by the lecithin concentration, the degree of saponification, and the mass ratio of indomethacin to pectin. The experiment results show that the lecithin has greatly improved the property of drug load and drug release of the gel microspheres in simulated intestinal fluid. With the mass ratio of PC to pectin 5:4, concentration of NaOH 30 g/L, mass ratio of IDM to pectin 1:4, drug release in simulated intestines is only 8.93% in 8 h. According to stability experiment, microspheres with lecithin were more stable at 60℃ or exposing to sunlight than that without lecithin. Observations from the present study reveals that optimized pectin-Zn-lecithin beads composited with lecithin can efficiently encapsulate indomethacin and have potential for colon-specific delivery to the lower gastrointestinal tract.