Plume temperature emitted from metered dose inhalers
Plume temperature emitted from metered dose inhalers
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DOI：
10.1016/j.ijpharm.2010.11.037
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发表时间：
2011-02-28
影响因子：
5.8
通讯作者：
Meakin, B.
中科院分区：
文献类型：
--
作者：
Brambilla, G.;Church, T.;Meakin, B.
加压计量吸入器(PMDI)释放的药物云的温度可能会导致患者不适，并向肺部提供不一致或不存在的剂量。配方(药物、推进剂、共溶剂含量)和设备硬件(计量体积、致动器孔口直径、附加设备)的变化对pMDI羽流温度的影响，以重复平均最小值(MMPT)表示，收集到药典剂量单位采样装置(DUSA)中。已经被调查过了。审查了包括氯氟烃悬浮剂和氢氟烷烃溶液或悬浮液在内的10种商用产品和2种开发产品，以及处于后期开发阶段的若干药物产品和各种HFA 134a安慰剂PMDIs。观察到，在产品执行机构喷嘴附近的羽流温度最低，在那里，配方推进剂和挥发性辅料的快速闪光和蒸发会导致冷却。确定了通过合理选择配方、共溶剂含量、计量体积和执行器孔口直径来控制羽流温度的能力。通过细孔输送的基于乙醇的HFA 134a配方固有地比100%HFA 134a通过粗大的致动器孔口输送的制剂更温暖。在所评价的10种商业产品中，MMPT的范围从-54摄氏度到+4摄氏度，遵循配方等级顺序、氢氟烷烃悬浮剂和氯氟烷烃悬浮液。对于所检查的所有系统，可以通过使用附加装置或集成间隔装置将pMDI羽流温度提高到环境温度。(C)2010爱思唯尔B.V.保留所有权利。
The temperature of the drug cloud emitted from a pressurised metered dose inhaler (pMDI) may result in patient discomfort and inconsistent or non-existent dose delivery to the lungs. The effects of variations in formulation (drug, propellant, co-solvent content) and device hardware (metering volume, actuator orifice diameter, add-on devices) upon the temperature of pMDI plumes, expressed as replicate mean minimum values (MMPT), collected into a pharmacopoeial dose unit sampling apparatus (DUSA). have been investigated. Ten commercially available and two development products, including chlorofluorocarbon (CFC) suspensions and hydrofluoroalkane (HFA) solutions or suspensions, were examined together with a number of drug products in late stage development and a variety of HFA 134a placebo pMDIs. Plume temperatures were observed to be lowest in the proximity of the product's actuator mouthpiece where rapid flashing and evaporation of the formulation's propellant and volatile excipients cause cooling. The ability to control plume temperature by judicious choice of formulation co-solvent content, metering volume and the actuator orifice diameter is identified. An ethanol based HFA 134a formulation delivered through a fine orifice is inherently warmer than one with 100% HFA 134a vehicle delivered through a coarse actuator orifice. Of the 10 commercial products evaluated, MMPTs ranged from -54 to +4 degrees C and followed the formulation class rank order, HFA suspensions < CFC suspensions < HFA solutions. For all systems examined it was possible to raise pMDI plume temperature to that of the ambient surroundings by use of an add-on or integrated spacer device. (C) 2010 Elsevier B.V. All rights reserved.