药学学报, 2019, 54(9): 1673-1679
引用本文:
孟胡齐, 陈岚, 陈东浩. 载体粒径与表面形态对胶囊型粉雾剂装置内处方分散的影响[J]. 药学学报, 2019, 54(9): 1673-1679.
MENG Hu-qi, CHEN Lan, CHEN Dong-hao. Effect of carrier size and surface morphology on the aerosolization of formulation in a capsule-based dry powder inhale[J]. Acta Pharmaceutica Sinica, 2019, 54(9): 1673-1679.

载体粒径与表面形态对胶囊型粉雾剂装置内处方分散的影响
孟胡齐1, 陈岚1,2, 陈东浩2
1. 上海理工大学医疗器械与食品学院, 上海 200093;
2. 杭州畅溪制药有限公司, 浙江 杭州 311121
摘要:
载体乳糖粒径及表面形态皆会对粉雾剂(dry powder inhaler)的分散结果造成影响。本研究将两种商用载体乳糖Lactohale 100®和Respitose SV003®(SV003)分别与马来酸氯苯那敏(chlorpheniramine maleate)混合作为制剂模型,通过快速筛选撞击器(fast screening impactor)分析两种载体处方在30和60 L·min-1流速下的体外沉积表现,同时使用计算流体力学(computational fluid dynamic,CFD)耦合离散元(discrete element modelling,DEM)方法探讨上述流速条件下两种载体颗粒在胶囊型粉雾剂装置Handihaler®内的运动情况。通过建立体外实验与模拟结果之间的联系,分析两种载体处方的分散特点及探讨Handihaler®装置结构的分散机制。体外实验和CFD-DEM结果表明,SV003载体处方在分散表现上更好。体外实验与CFD-DEM的比对结果显示,载体处方的微细颗粒剂量(fine particle dose)与载体颗粒和装置壁面的碰撞能量损失总和之间具有一定的线性相关性(R2=0.940 1),说明在Handihaler®分散结构内载体颗粒和壁面之间的碰撞作用会直接影响载体处方的分散结果。
关键词:    辅料      颗粒大小      表面特征      计算机模拟      吸入粉雾剂     
Effect of carrier size and surface morphology on the aerosolization of formulation in a capsule-based dry powder inhale
MENG Hu-qi1, CHEN Lan1,2, CHEN Dong-hao2
1. School of Medical Instrument and Food Engineering, University of Shanghai for Science and Technology, Shanghai 200093, China;
2. Hangzhou Chance Pharmaceuticals Co. Ltd., Hangzhou 311121, China
Abstract:
The size and surface morphology of carrier lactose had influence on the aerosolization performance of dry powder inhalers. In this article, chlorpheniramine maleate was blended with two types of commercial carrier lactose, which were Lactohale 100® and Respitose SV003® (SV003), as formulation model. In vitro experiments were conducted using fast screening impactor at 30 L·min-1 and 60 L·min-1 respectively. Meanwhile, computational fluid dynamics (CFD) coupling with discrete element modelling (DEM) was applied to discuss the movements of those two carrier particles in Handihaler® at the flow rate mentioned above. The dispersion characteristics of two formulations and the dispersion mechanism of Handihaler® were analyzed by establishing the relationship between in vitro experiments and numerical simulation. The results of in vitro experiments and CFD-DEM demonstrated that the aerosolization performance of formulation with SV003 was better. The linear correlation (R2=0.940 1) between fine particle dose and total energy loss by carrier collision within the wall of device was found by comparing the in vitro experimental results with CFD-DEM results. It revealed that particle-wall collision in Handihaler® had direct impact on the dispersion results of formulation.
Key words:    excipient    particle size    surface property    computer simulation    dry powder inhaler   
收稿日期: 2019-06-04
DOI: 10.16438/j.0513-4870.2019-0444
通讯作者: 陈岚,Tel:86-21-55271200,Fax:86-21-55270695,E-mail:lanchen@usst.edu.cn
Email: lanchen@usst.edu.cn
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