不同含水量胶囊壳对吸入粉雾剂体外分散效果的影响

Effect of Capsule Shells with Different Moisture Contents on in vitro Dispersion of Dry Powder Inhaler

本研究以明胶胶囊壳和羟丙甲纤维素(HPMC)胶囊壳为研究对象,分别在低、中、高3种相对湿度环境中放置15 d,制得不同含水量的胶囊壳,考察了不同含水量胶囊壳的物理性能差异。再将乳糖Respitose SV003和ML001分别与马来酸氯苯那敏混合,作为模型处方,立即灌入不同含水量和不同材质的胶囊壳中,以Breezhaler®为吸入装置,使用快速筛选撞击器对所得吸入粉雾剂(DPI)的体外沉积进行评价。结果表明,在毛细管力和静电力的共同作用下,采用含水量过高或过低的胶囊壳制备的DPI,胶囊内残留药量和预分离器中药物沉积量均较高,造成微细粒子剂量(FPD)下降;在高含水量条件下,HPMC胶囊壳的分散性能优于明胶胶囊壳;但当2种胶囊壳的含水量均适中时,胶囊材质对相同处方的体外分散性能几乎没有影响。由于乳糖ML001含有较多细粉、较大的表面粗糙度,所以该处方具有更优异的体外分散表现。

In this paper,gelatin and hydroxypropyl methylcellulose(HPMC)capsule shells were selected as research subjects,then they were respectively stored under low,middle and high relative humidity conditions for 15 d to obtain the test capsule shells with different moisture contents for evaluating the difference in physical properties.Furtherly,dry powder inhaler(DPI)of chlorpheniramine maleate based on Breezhaler®device were prepared by immediately filling the mixture of drug and lactose carrier(Respitose SV003 or ML001)into the above gelatin and HPMC capsule shells with different moisture contents.Their in vitro deposition profiles were investigated by fast screening impactor(FSI).The results showed that both the residual amount in capsules and deposition in preseparator of drug from DPI prepared by capsule shells with high or low moisture contents were higher due to the combination of the capillary force and electrostatic force,thus resulting in the decline of fine particle dose(FPD).Under the high moisture content condition,the dispersion performance of HPMC capsule shells was superior to that of gelatin capsule shells.However,almost no differences were observed in dispersion performance for the same formulation when gelatin and HPMC capsule shells contained moderate moisture content.The formulation with ML001 performed better in dispersion,due to the more content of the fine lactose powder and the greater surface roughness of ML001.