Box-Behnken效应面法优化美洛昔康纳米晶舌下速溶膜的处方研究  

Optimization of Meloxicam Nanosuspensions Fast Dissolving Sublingual Films(MLX-NS-Fdsfs) by Box-Behnken Response Surface Methodology

作　　者：徐方楚[1] 沈成英[1] 连王权 申宝德[1,2] 卢丽琨[1] 马亚中[1] 袁海龙[1] 

机构地区：[1]空军总医院药学部,北京100142 [2]江西中医药大学药学院,南昌330004

出　　处：《中国药学杂志》2018年第1期46-51,共6页Chinese Pharmaceutical Journal

基　　金：全军后勤科研重点项目资助(BKJ16J011);全军重大科研计划资助(BKJ16J025)

摘　　要：目的制备美洛昔康纳米晶舌下速溶膜(MLX-NS-FDSFs),优化其处方,并考察其体外溶出。方法采用pH依赖的溶解沉淀联合高速剪切法制备美洛昔康纳米晶(MLX-NS),进一步制成舌下速溶膜。以羟丙甲基纤维素E30(HPMC-E30)质量浓度、聚乙二醇400(PEG-400)质量浓度和MLX-NS加入体积为考察因素,以膜复溶后纳米粒的粒径、崩解时间和拉伸长度为指标,采用Box-Behnken设计试验优化MLX-NS-FDSFs处方。考察以最优处方制备的MLX-NS-FDSFs的形态、含量均匀度和体外溶出度。结果以最优处方35 mg·mL^(-1)HPMC-E30、40 mg·mL^(-1)PEG-400、10 mL MLX-NS制得的MLX-NS-FDSFs复溶后的纳米粒粒径为(186.4±6.3)nm,崩解时间为(26.08±1.76)s、拉伸长度为(1.51±0.13)mm,理论预测值与实测值偏差较小,模型具有良好的预测性。形态分析结果显示,MLX纳米粒均匀的分散在膜内,含量均匀度符合规定,MLX在5 min内释放度达到(91.75±8.05)%。结论采用Box-Behnken效应面法优化MLX-NS-FDSFs处方是可行、有效的,MLX-NS-FDSFs可显著提高MLX的累积溶出度。OBJECTIVE To prepare and optimize meloxicam nanosuspensions fast dissolving sublingual films （MLX-NS-FDSFs） and to evaluate its in vitro dissolution characteristics. METHODS Meloxicam nanosuspensions （MLX-NS） were prepared by pH-dependent dissolving-precipitating/high speed shearing method and then transformed into fast dissolving sublingual films （FDSFs）. The formulations of MLX-NS-FDSFs were optimized by employing Box-Behnken design-response surface methodology with the amount of HPMC-E30, PEG-400 and MLX-NS as investigation factors, and particle size of reconstituted nanoparticles from MLX-NS-FDSFs, disintegration time and stretch length as indexes. The morphology, content uniformity and in vitro dissolution of the optimal formulation were also evaluated. RESULTS The MLX-NS-FDSFs prepared by optimized formulation （35 mg·m L^-1 HPMC-E30, 40 mg ·m L^-1 PEG-400, 10 mL MLX-NS） could fast disintegrate in （26.08 ± 1.76） s, the tensile length was （1.51 ±0. 13） mm, and the particle size of reconstituted nanoparticles from MLX-NS-FDSFs was （186. 4 ± 6.3 ） nm. There was a little deviation between the theoretically predicted value and the measured value. It showed that this model had a good prediction. Morphological analysis showed that well-dis- persed MLX nanoparticles embedded in MLX-NS-FDSFs. The conformity of drug content was up to standard. MLX could be released in vitro as much as （91.75 ± 8.05） % within five minutes. CONCLUSION Using Box-Behnken design and response surface method to optimize MLX-NS-FDSFs is effective and feasible. MLX-NS-FDSFs can significantly increase the cumulative dissolution of MLX.

关 键 词：美洛昔康 纳米晶 舌下速溶膜 BOX-BEHNKEN效应面法 体外溶出度 

分 类 号：R944[医药卫生—药剂学]