粉雾剂装置吸嘴插入口腔方位对药物递送影响研究

Effect of the DPI Mouthpiece Position in Mouth on Drug Delivery Performance

摘要: 目的：研究粉雾剂(Dry Powder Inhaler, DPI)吸入装置吸嘴插入口腔的方位对药物递送、沉积表现等性能的影响。方法：以布地奈德为原料药，制备载体型处方模型；借助体外NGI (Next Generation Impactor, NGI)撞击器实验结果获得仿真所需要的药物粒径分布参数；两种吸入装置RS01和Handihaler在各自的高、中、低三种流速条件下，分别对吸嘴插入口腔不同方位的药物递送情况进行数值模拟研究。结果：吸嘴的插入方位明显影响口喉等上游气道流场分布，对主支气管以下区域流场影响较小；另外，口喉部的药物沉积影响与吸入装置类型及吸气流速有关：若以“插入角度30˚，插入深度5 mm”条件下的沉积量为基准，对于RS01装置，吸嘴插入方位变化引起的口喉沉积差异在低流速条件下为8%⁓116%，在高流速条件下为5.32%⁓20.41%，而Handihaler在低流速条件下为14.22%⁓17.39%，在高流速条件下为2.31%⁓8.46%。结论：在吸气流速不变的情况下，吸嘴插入方位改变会引起口喉等上呼吸道流场差异，文中两种吸入装置表现一致；吸嘴插入方位对口喉沉积的影响与吸入装置类型及吸气流速大小有关，RS01吸嘴插入方位改变对口喉沉积的影响在低流速条件下非常明显，而Handihaler影响程度则较小。因此对于不同的粉雾剂装置，吸嘴与口部的方位情况值得深入探讨。

Abstract: Objective: To study the influence of the positions of the mouthpiece of the dry powder inhaler in the mouth on the delivery and deposition of the medicine. Methods: Budesonide was used as an active pharmaceutical ingredient for a carrier-based prescription model. The particle size distribution of the drugs required for the simulation was obtained from the in vitro NGI impactor experience. Un-der the conditions of high, medium and low flow of RS01 and Handihaler, the drug delivery perfor-mance of different mouthpiece positions in the mouth was numerically simulated. Results: The po-sitions of the mouthpiece in the mouth primarily affects the distribution of the flow field of the up-per airways such as the mouth and throat, but has little effect on the flow field under the main bronchial. In addition, the influence of the position of the mouthpiece in the mouth on the deposit of drugs in the mouth and throat is related to the type of device and the breathing rate. When the de-posit amount in the condition “insertion angle 30˚, insertion depth 5 mm” is taken as a reference, for RS01 device, the mouthpiece positions in the mouth caused a regional quantitative change in drug deposit in a low flow condition is 8%⁓116%, in a high flow condition for 5.32%⁓20.41%; How-ever, Handihaler is 14.22%⁓17.39% at low flow rate and 2.31%⁓8.46% at high flow rate. Conclu-sion: Under the condition of constant inspiratory flow rate, the orientation of the mouthpiece mainly affects the flow field distribution of the upper respiratory tract such as the mouth and throat, the two inhalation devices in this paper have the same performance; The influence of the position of the mouthpiece in the mouth on the deposit of the mouth and throat is linked to the type of inhaler and the inspiratory flow, the effect of changing the insertion position of the RS01 mouthpiece on the mouth and throat deposit was very evident at low flow rates, whereas the effect of Handihaler was less significant. Consequently, for various DPI devices, the positions of the mouthpieces in the mouth deserve a thorough discussion.