Everard M L, Devadason S G, Le Souef P N
Department of Respiratory Medicine, Princess Margaret Hospital for Children, Perth, Western Australia.
Thorax. 1996 May;51(5):537-9. doi: 10.1136/thx.51.5.537.
Drug deposited within the upper airways of patients using dry powder inhalers does not contribute to the therapeutic effect but can result in unwanted local side effects and, when swallowed, may contribute to systemic effects. A chamber has been devised which uses the centrifugal force generated by the Turbohaler to remove large "non-respirable" particles with a view to minimising deposition in the upper airway. An in vitro study was performed to determine whether such a chamber could reduce the dose contained in coarse particles without having a significant effect on the "respirable dose".
The mouthpiece of a 200 micrograms Turbohaler was modified to allow a small volume chamber to be attached. The particle size distribution generated by the Turbohaler was assessed using a multi-stage liquid impinger with a flow rate of 60 l/min. The quantity of drug on each stage was quantified using an ultraviolet spectrophotometric technique. For each experiment 10 actuations were used to ensure adequate quantities of drug on each stage. Particles depositing on stages 3 + 4 have a diameter of < 6.8 microns and are arbitrarily referred to as the "respirable dose". The particle size distribution obtained using the Turbohaler (n = 10) was compared with that from the Turbohaler+ chamber (n = 11).
The addition of the chamber resulted in the mean (SD) dose contained in larger "non-respirable" particles depositing on stages 1 + 2 being reduced from 52.2 (12.3) to 29.6 (6.9) micrograms per actuation. However, the chamber did not affect the "respirable" dose. The dose contained in particles with a diameter of < 6.8 microns from the standard Turbohaler was 91.1 (8.9) micrograms compared with 82.4 (18.6) micrograms when used with the chamber.
These results indicate that it is possible to devise an effective particle size selection device for the Turbohaler. It may be possible to produce such devices for other dry powder inhalers, although the design would need to be tailored to each particular device.
使用干粉吸入器的患者，药物沉积在上呼吸道中对治疗效果无贡献，但会导致不必要的局部副作用，且吞咽后可能产生全身作用。已设计出一种腔室，利用都保产生的离心力去除大的“不可吸入”颗粒，以尽量减少在上呼吸道的沉积。进行了一项体外研究，以确定这种腔室能否减少粗颗粒中的药物剂量，同时又不显著影响“可吸入剂量”。
对200微克都保的吸嘴进行改造，以便连接一个小容量腔室。使用流速为60升/分钟的多级液体冲击器评估都保产生的颗粒大小分布。采用紫外分光光度技术对每个阶段的药物量进行定量。每次实验使用10次揿压，以确保每个阶段有足够量的药物。沉积在第3 + 4阶段的颗粒直径<6.8微米，被任意称为“可吸入剂量”。将使用都保（n = 10）获得的颗粒大小分布与使用都保+腔室（n = 11）获得的进行比较。
添加腔室后，沉积在第1 + 2阶段的较大“不可吸入”颗粒中的平均（标准差）剂量从每次揿压52.2（12.3）微克降至29.6（6.9）微克。然而，腔室并未影响“可吸入”剂量。标准都保产生的直径<6.8微米颗粒中的剂量为91.1（8.9）微克，与使用腔室时的82.4（18.6）微克相比。
这些结果表明，有可能为都保设计一种有效的颗粒大小选择装置。虽然设计需要针对每个特定装置进行调整，但有可能为其他干粉吸入器生产此类装置。
