摘要
研制一种能改善膜剂载药量的新剂型——银杏内酯B纳米混悬冻干粉速溶膜(GB-NS-LP-ODF),并对其进行质量评价。采用介质研磨法制备银杏内酯B纳米混悬剂(GB-NS),冷冻干燥法制备银杏内酯B纳米混悬冻干粉(GB-NS-LP),以甘露醇为冻干保护剂并考察其用量;采用溶剂浇铸法制备GB-NS-LP-ODF,单因素试验法筛选其处方,正交试验进一步优化处方用量,并对其外观、机械性能、含量均匀度和体外溶出度等进行考察。制备的GB-NS粒径约为201 nm,甘露醇最佳用量为8.0%;以最优处方:GB-NS-LP 35.6%,PVA 0588 49.4%,PEG 400 10.7%,CMS-Na 4.3%制备的GB-NS-LP-ODF在30 s左右完全崩解,复溶粒径约为210 nm;膜剂外观平整光滑,机械性能良好,在30 d内稳定性良好,含量均匀度(A+2.2S<15)符合规定;扫描电镜(SEM)显示GB-NS-LP-ODF分布均匀,粒径约为200 nm,X射线衍射(XRD)显示其结晶度较GB原料药和GB-ODF显著降低;体外释放研究显示药膜在10 min内释药完全。结果表明将纳米混悬剂冻干处理后制备为纳米混悬冻干粉,进一步载入速溶膜剂,可有效提高膜剂的载药量,具有广阔的应用前景。
To prepare a new dosage form that can improve the drug loading of the film--ginkgolide B nanosuspension lyophilized powder orodispersible film(GB-NS-LP-ODF) and to evaluate its quality. Firstly, ginkgolide B nanosuspension(GB-NS) was prepared by media milling method, and then ginkgolide B nanosuspension lyophilized powder(GB-NS-LP) was prepared with freeze-drying method. The mannitol was used as lyoprotectant and its dosage was also investigated. GB-NS-LP-ODF was prepared by solvent casting method and its formulation was screened by single factor test method and optimized by orthogonal test. The appearance, mechanical properties, content uniformity and in vitro dissolution of the optimized GB-NS-LP-ODF were investigated. The particle size of prepared GB-NS was about 201 nm, and the optimal dosage of mannitol was 8%. According to the optimal formula, the GB-NS-LP-ODF was prepared with GB-NS-LP 35.6%, PVA 0588 49.4%, PEG 400 10.7% and CMS-Na 4.3%, and completely disintegrated in about 30 s, and the particle size of reconstituted GB nanoparticles from ODF was about 210 nm. The film with smooth appearance and good mechanical properties was stable within 30 days and the content uniformity(A+2.2 S<15) conformed to the regulations. Scanning electron microscope(SEM) showed that GB-NS-LP-ODFs were evenly distributed and the particle size was about 200 nm. X-rays diffraction(XRD) showed that its crystallinity was significantly lower than that of GB raw drug and GB-ODF. The results of in vitro release test showed that the drug film was completely dissoluted within 10 minutes. These results indicated that nanosuspension lyophilized powder was prepared by freeze drying of nanosuspensions, and then loaded into the orodispersible film to effectively increase the drug loading of the ODF and have broad application prospects.
作者
王镜
朱君君
申宝德
张婷
戴博
朱雅宁
袁海龙
WANG Jing;ZHU Jun-jun;SHEN Bao-de;ZHANG Ting;DAI Bo;ZHU Ya-ning;YUAN Hai-long(College of Pharmacy,Chengdu University of Traditional Chinese Medicine,Chengdu 611137,China;Department of Pharmacy,Air Force Medical Center,PLA,Bejing 100142,China)
出处
《中国中药杂志》
CAS
CSCD
北大核心
2020年第22期5504-5510,共7页
China Journal of Chinese Materia Medica
基金
军队后勤科研重点项目(BKJ16J011)
全军医学科技青年培育计划拔尖项目(17QNP028)。
关键词
银杏内酯B
纳米混悬剂
冷冻干燥
口腔速溶膜
质量评价
累积溶出度
ginkgolide B
nanosuspension
freezedrying
orodispersible film
quality evaluation
cumulative dissolution
