乳化溶剂挥干法制备水溶性羧化壳聚糖鼻用微球及其特性的考察

Preparation of Zolmitriptan Water-Soluble Carboxylation Chitosan Microspheres for Nasal Delivery by Emulsification Solvent Evaporation Method and Its Characteristics Evaluation

目的为避免传统制备壳聚糖微球过程中使用对人体具有刺激性和毒性的酸性溶剂及醛类交联剂,提高制剂鼻腔给药的生物相容性,本实验采用水溶性羧化壳聚糖为药物载体材料,通过乳化溶剂挥干法制备鼻用微球。方法以佐米曲普坦为模型药物,考察处方工艺因素的改变对载佐米曲普坦的羧化壳聚糖微球特性的影响,并筛选出微球的最佳处方和制备工艺,进而对微球的收率、粒径、外观、载药量、包封率以及释放行为等进行评价。结果所得微球呈球形,表面光滑,流动性较好,粒径分布较为均匀,平均粒径为(21.4±10.1)μm,载药量为5.67%,包封率为62.4%,体外释放研究表明微球具有一定的缓释作用。结论乳化溶剂挥干法制备羧化壳聚糖鼻用微球是可行的,可避免酸性溶剂及醛类毒性交联剂的使用。

OBJECTIVE To prepare microspheres for nasal delivery by emulsification solvent evaporation technique using watersoluble carboxylatiou chitosan as the drug carrier, thus to avoid using stinmlatory and toxic aldehydes crosslinkers and acid solventwhich are used by the traditional method. METHODS Zolmitriptan （ZT） was used as the model drug to prepare the carhoxylationchitosan microspheres. The prescription and technology were optimized to prepare the microspheres. The yield, particle sizes, appearance,drug loading, encapsulation efficiency and drug release of the microspheres were evaluated. RESULTS The microspheres prepared by the optimized method were spherical, smooth, and free flowing. The particle sizes of the microspheres were well-distributed and the mean particle size was （21.4 ± 10. 1 ） μm. The drug loading was 5.67% and the encapsulation efficiency was 62. 4%. The invitro release study of the microspheres showed that the drug was sustainedly released and could be released for about 85% in 8 h. CONCLUSION It is feasible to prepare carboxylation chitosan microspheres for nasal administration by emulsification solvent evapo-ration method, avoiding the use of aldehydes crosslinkers and acid solvent.