Tang Patricia, Leung Sharon S Y, Hor Eleanor, Ruzycki Conor A, Carrigy Nicholas B, Finlay Warren H, Brannan John D, Devadason Sunalene, Anderson Sandra D, Sly Peter D, Samnick Kevin, Chan Hak-Kim
1 Advanced Drug Delivery Group, Faculty of Pharmacy, The University of Sydney , Sydney, New South Wales, Australia .
2 Department of Mechanical Engineering, University of Alberta , Edmonton, Canada .
J Aerosol Med Pulm Drug Deliv. 2015 Dec;28(6):452-61. doi: 10.1089/jamp.2015.1208. Epub 2015 Apr 6.
Currently bronchial provocation testing (BPT) using mannitol powder cannot be performed in children under 6 years. A primary reason is it is challenging for children at this age to generate a consistent inspiratory effort to inhale mannitol efficiently from a dry powder inhaler. A prototype system, which does not require any inhalation training from the pediatric subject, is reported here. It uses an external source of compressed air to disperse mannitol powder into a commercial holding chamber. Then the subject uses tidal breathing to inhale the aerosol.
The setup consists of a commercially available powder disperser and Volumatic™ holding chamber. Taguchi experimental design was used to identify the effect of dispersion parameters (flow rate of compressed air, time compressed air is applied, mass of powder, and the time between dispersion and inhalation) on the fine particle dose (FPD). The prototype was tested in vitro using a USP throat connected to a next generation impactor. The aerosols from the holding chamber were drawn at 10 L/min. A scaling factor for estimating the provoking dose to induce a 15% reduction in forced expiratory volume in 1 second (FEV1) (PD15) was calculated using anatomical dimensions of the human respiratory tract at various ages combined with known dosing values from the adult BPT.
Consistent and doubling FPDs were successfully generated based on the Taguchi experimental design. The FPD was reliable over a range of 0.8 (±0.09) mg to 14 (±0.94) mg. The calculated PD15 for children aged 1-6 years ranged from 7.1-30 mg. The FPDs generated from the proposed set up are lower than the calculated PD15 and therefore are not expected to cause sudden bronchoconstriction.
A prototype aerosol delivery system has been developed that is consistently able to deliver doubling doses suitable for bronchial provocation testing in young children.
目前，使用甘露醇粉末的支气管激发试验（BPT）无法在6岁以下儿童中进行。一个主要原因是，这个年龄段的儿童要产生持续一致的吸气动作，以便从干粉吸入器中有效吸入甘露醇具有挑战性。本文报道了一种原型系统，该系统无需儿科受试者进行任何吸入训练。它使用外部压缩空气源将甘露醇粉末分散到一个商用储存腔室中。然后受试者通过潮式呼吸吸入气雾剂。
该装置由一个市售的粉末分散器和Volumatic™储存腔室组成。采用田口实验设计来确定分散参数（压缩空气流速、压缩空气施加时间、粉末质量以及分散与吸入之间的时间）对细颗粒剂量（FPD）的影响。该原型在体外使用连接到下一代撞击器的美国药典咽喉模型进行测试。来自储存腔室的气雾剂以10升/分钟的流速抽取。使用不同年龄人类呼吸道的解剖尺寸结合成人BPT的已知给药值，计算出估计能使一秒用力呼气量（FEV1）降低15%的激发剂量（PD15）的缩放因子。
基于田口实验设计成功产生了一致且成倍增加的FPD。FPD在0.8（±0.09）毫克至14（±0.94）毫克的范围内可靠。1至6岁儿童计算出的PD15范围为7.1至30毫克。所提出的装置产生的FPD低于计算出的PD15，因此预计不会引起突然的支气管收缩。
已开发出一种原型气雾剂输送系统，该系统能够持续输送适合幼儿支气管激发试验的成倍剂量。
