富马酸福莫特罗口腔速溶膜剂的制备和评价  

Formulation development and evaluation of oral fast dissolving films of formoterol fumarate

作　　者：周烨 金怡兰 顾悦 宗亚玲 陈勇 ZHOU Ye;JIN Yilan;GU Yue;ZONG Yaling;CHEN Yong(School of Pharmacy,Nantong University,Nantong 226001;Department of Pharmacy,the Third Affiliated Hospital of Shandong First Medical University;Novast Pharmaceu-ticals,Ltd.)

机构地区：[1]南通大学药学院,南通226001 [2]山东第一医科大学第三附属医院药剂科 [3]南通联科药业有限公司

出　　处：《南通大学学报（医学版）》2021年第1期15-19,共5页Journal of Nantong University(Medical sciences)

基　　金：中国博士后科学基金资助项目(2017M611886)。

摘　　要：目的:制备并评价富马酸福莫特罗口腔速溶膜剂(formoterol fumarate oral fast dissolving films, FMT-OFDF)。方法:采用溶剂浇铸法制备FMT-OFDF。以羟丙甲纤维素E5(hydroxypropyl methylcellulose E5, HPMC E5)、甘油和预胶化淀粉的用量为考察因素,以膜剂的外观、厚度和崩解时间为评价指标,用正交试验法优化处方;对制备的FMT-OFDF的厚度、含量均匀度、含水量、折叠耐力、表面pH值、体外崩解时间和体外溶出等指标进行评价;通过扫描电镜及X射线衍射考察FMT在膜剂中的存在状态。结果:筛选的最优处方为HPMC E5(0.30 g)、甘油(0.10 g)和预胶化淀粉(0.01 g)。制备的FMT-OFDF的厚度为(65.37±0.61)μm,FMT含量为(44.33±2.01)μg,含水量为(5.73±0.27)%,折叠耐力为(236.70±7.09)次,崩解总时长为(57.60±3.01) s,表面pH值为6.83±0.11,在3 min时FMT的累积释放可达99.24%。FMT-OFDF的表面无原料药颗粒,无微观损伤,FMT在OFDF中以分子形式存在。结论:采用正交试验法优化制得的FMT-OFDF外观光滑透明,崩解迅速,表明FMT-OFDF有快速缓解哮喘的潜力。Objective:The objective was to prepare and evaluate formoterol fumarate oral fast dissolving films(FMT-OFDF).Methods:FMT-OFDF was prepared by solvent casting method.The formulation of FMT-OFDF was optimized by employing orthogonal design,in which the amounts of hydroxypropyl methylcellulose E5(HPMC E5),glycerol and pregelatinized starch were served as investigation factors.Film thickness,physical appearance,content uniformity,water content,folding endurance,surface pH,in vitro disintegration time and in vitro dissolution of the FMT-OFDF were evaluated.Scanning electron microscopy and X-ray diffraction were examined to investigate the physical state of FMT in the film.Results:The optimal formulation was HPMC E5(0.30 g),glycerol(0.10 g)and pregelatinized starch(0.01 g).The thickness of the film was(65.37±0.61)μm,the drug content of each film was(44.33±2.01)μg,the water content was(5.73±0.27)%,the folding endurance was(236.70±7.09)times,the total disintegration time was(57.60±3.01)s,and the surface pH was about 6.83±0.11.The cumulative release of FMT can reach 99.24%at 3 min.No particles and microscopic damage were observed on the surface of FMT-OFDF.FMT was dispersed in the OFDF in molecular state.Conclusion:The FMT-OFDF,whose composition was optimized by employing orthogonal design,had a smooth surface,good transparency and rapid disintegration speed,suggesting a potential for rapid alleviation of asthma by oral dosing.

关 键 词：富马酸福莫特罗 口腔速溶膜剂 正交试验 溶剂浇铸法 

分 类 号：R94[医药卫生—药剂学]