粉雾剂胶囊的穿刺特性与体外分散表现评价

Evaluation of Puncture Characteristics and in vitro Dispersion Performance of Capsules for Dry Powder Inhaler

本试验探究了粉雾剂(dry powder inhaler,DPI)装置中明胶和羟丙甲纤维素(hydroxypropyl methylcellulose,HPMC)2种材质胶囊在不同轴直径刺针及穿刺速度条件下的力学性能表现,及对药物体外分散沉积效果的影响。穿刺性能测试使用的是装有单根DPI刺针的质构仪,研究了不同轴直径(0.58、1.17和1.46 mm)刺针和穿刺速度(0.05和5 mm/s)对2种胶囊刺破力和穿刺效果的影响。此外,还在60 L/min的流速下,使用快速筛选撞击器进行了体外分散试验,研究胶囊材质和刺针尺寸对DPI体外分散行为的影响。结果显示,HPMC胶囊与明胶胶囊相比,所需的刺破力更小,不易产生胶囊壳碎片;穿刺速度对胶囊上穿刺形成的孔洞面积影响较小。分散试验结果表明,与明胶胶囊相比,马来酸氯苯那敏在HPMC胶囊内残余量更少,微细粒子剂量(fine particle dose,FPD)相对较大。本研究的3种刺针中,0.58 mm直径的刺针穿刺胶囊产生的孔洞最小,药物在预分离器中沉积量最少,所得的FPD值最大,说明适当减小刺孔的尺寸有可能更有利于药物分散,但明胶胶囊有可能产生胶囊壳碎片。以上研究结果将为胶囊型DPI产品开发中胶囊材质的选择和刺针尺寸的确定提供技术参考。

The effects of gelatin capsules and hydroxypropyl methylcellulose(HPMC) capsules for dry powder inhaler(DPI) on puncture mechanical property and in vitro dispersion performance were investigated. The puncture test was carried out by a texture analyzer with one piercing needle. The effects of needles with different dimeters of 0.58, 1.17 and 1.46 mm and puncture speed(0.05 and 5 mm/s) on puncture force and hole size in two types of capsule were investigated. Additionally, the in vitro dispersion experiment was carried out by the fast screening impactor(FSI) at a flow rate of 60 L/min. So, the influences of capsule material and piercing needle size on in vitro dispersion behavior were assessed. The results showed that HPMC capsules had the advantages of less puncture force and fewer capsule shell fragments compared with gelatin capsules at the same conditon, and puncture speed had little effect on hole size in capsules. The results of dispersion experiment indicated that chlorpheniramine maleate had less retention in HPMC capsules and greater fine particle dose(FPD) compared with gelatin capsules. Among the tested three needles, the needle with diameter of 0.58 mm made the smallest holes, resulting in the least deposition in the pre-separator and the largest FPD value, which indicated that the proper reduction of the puncture hole size might be more conductive to drug dispersion but increased the probability of gelatin fragment-forming. This research may provide technical references for selection of capsule material and piercing needle size in development of capsule-based DPI.