离子交联-喷雾干燥联用技术制备鼻用黄芩苷微球及其体外性能评价  

Preparation and in Vitro Characterization of Baicalin Microspheres for Intranasal Administraion by Ionic Crosslinking Coupled with Spray-drying Method

作　　者：屈娜[1] 郭立玮[1] 朱华旭[1] 鞠凤[1] 李博[1] 付廷明[1] 潘林梅[1] 

机构地区：[1]南京中医药大学江苏省中药资源产业化过程协同创新中心江苏省植物药深加工工程研究中心,南京210023

出　　处：《中国实验方剂学杂志》2016年第7期1-5,共5页Chinese Journal of Experimental Traditional Medical Formulae

基　　金：国家自然科学基金项目(81072749;81303230;30873449;30873450);江苏省科技厅自然科学基金项目(BK 2012855);江苏省科技厅产学研联合创新资金--前瞻性研究项目(BY 2012036);江苏省六大人才高峰项目(2014-YY-014);江苏省高校优势学科建设工程项目;江苏省中药资源产业化过程协同创新中心项目(ZDXM)

摘　　要：目的:制备鼻用干粉吸入剂,探讨以壳聚糖为载体的黄芩苷纳米粒组装成微球的制备方法及其体外释放性能、鼻黏膜渗透性。方法:采用离子交联法制备黄芩苷壳聚糖纳米粒,利用喷雾干燥法将纳米粒组装成微球。利用扫描电镜、差示扫描量热及X射线衍射等对微球进行表征,考察其在人工鼻电解质液中的体外释放性能及模拟人鼻黏膜条件下的鼻黏膜渗透性。结果:黄芩苷纳米粒(一级粒子)平均粒径(170.5±2.3)nm,纳米粒经喷雾干燥后形成平均粒径(6.8±0.4)μm的微球(二级粒子),药物以无定形态分布于载体材料中,微球比流动能(5.46±0.37)m J·g-1。在正应力15 k Pa时,空气以2 mm·s-1的速度通过微球粉末时气压降值0.323 k Pa。该粒子遇人工鼻电解质溶液后能重新分散,释放出一级粒子。体外释放表明微球33 h累积释放率(78.85±2.71)%,体外释药过程符合Riger-Peppas模型。微球在7 h时单位面积累计释放量为黄芩苷原料药的1.77倍。结论:制备的黄芩苷微球能够释放出一级粒子,具有较好的流动性、透气性和一定缓释作用,可提高黄芩苷的透鼻黏膜性。Objective： To prepare nasal dry powder inhaler,preparation of microspheres which assembled by baicalin nanoparticles with chitosan as carrier, in vitro release properties and nasal mucous membrane permeability were invesgated. Method： Primary nanoparticles were prepared by ionic cross-linking,nanoparticles were assembled to microspheres by spray drying method. Particles were characterized by scanning electron microscopy（ SEM）,X-ray diffraction（ XRD）,differential scanning calorimetry（ DSC） and so on,its in vitro release in artificial nose liquid electrolyte and permeability under simulated human nasal mucosa were investigated. Result： Average particle size of primary particles was（ 170. 5 ± 2. 3） nm,while the second particles was（ 6. 8 ± 0. 4） μm with drug dispersed as amorphous form in them. Specific energy of microspheres was（ 5. 46 ±0. 37） m J·g- 1,pressure drop was 0. 323 k Pa when air kept speed of 2 mm·s- 1through powder bed with force was 15 k Pa. And the second particles could decomposed into primary nanoparticles in simulated nasal electrolyte solution.Cumulative release rate of baicalin was（ 78. 85 ± 2. 71） % in 33 hours and release curve accorded with Riger-Peppas model. Value of cumulative release rate per unit area of microsphere was 1. 77 times that of the pure baicalin sample.Conclusion： These prepared microspheres can release primary particles with good fluidity, permeability and a certain sustained-release effect,it can improve nasal mucous membrane permeability of baicalin.

关 键 词：黄芩苷 离子交联法 喷雾干燥 微球 鼻腔给药 

分 类 号：R283.6[医药卫生—中药学] R945[医药卫生—中医学]