de Boer A H, Gjaltema D, Hagedoorn P, Schaller M, Witt W, Frijlink H W
Department of Pharmaceutical Technology and Biopharmacy, Groningen University Institute for Drug Exploration (GUIDE), University of Groningen, Antonius Deusinglaan 1, 9713 AV, Groningen, The Netherlands.
Int J Pharm. 2002 Dec 5;249(1-2):233-45. doi: 10.1016/s0378-5173(02)00527-6.
An inhaler adapter has been designed for the characterization of the aerosol clouds from medical aerosol generators such as nebulizers, dry powder inhalers (dpis) and metered dose inhalers (mdis) with laser diffraction technology. The adapter has a pre-separator, for separation of large particles (i.e. carrier crystals) from the aerosol cloud before it is exposed to the laser beam. It also has a fine particle collector for measuring the emitted mass fraction of fines by chemical detection methods after laser diffraction sizing. The closed system enables flow control through the aerosol generators and all test conditions, including ambient temperature and relative humidity, are automatically recorded. Counter flows minimize particle deposition onto the two windows for the laser beam, which make successive measurements without cleaning of these windows possible. The adapter has successfully been tested for nebulizers, mdis and dpis. In a comparative study with ten nebulizers it was found that these devices differ considerably in droplet size (distribution) of the aerosol cloud for the same 10% aqueous tobramycin solution (volume median diameters ranging from 1.25 to 3.25 microm) when they are used under the conditions recommended by the manufacturers. The droplet size distribution generated by the Sidestream (with PortaNeb compressor) is very constant during nebulization until dry running of the device. Comparative testing of dpis containing spherical pellet type of formulations for the drug (e.g. the AstraZeneca Turbuhaler) with the adapter is fast and simple. But also formulations containing larger carrier material could successfully be measured. Disintegration efficiency of a test inhaler with carrier retainment (acting as a pre-separator) could be measured quite accurately both for a colistin sulfate formulation with 16.7% of a lactose fraction 106-150 microm and for a budesonide formulation with a carrier mixture of Pharmatose 325 and 150 M. Therefore, it is concluded that, with this special adapter, laser diffraction may be a valuable tool for comparative inhaler evaluation, device development, powder formulation and quality control. Compared to cascade impactor analysis, laser diffraction is much faster. In addition to that, more detailed and also different information about the aerosol cloud is obtained.
已设计出一种吸入器适配器，用于通过激光衍射技术对来自诸如雾化器、干粉吸入器（DPI）和定量吸入器（MDI）等医用气雾剂发生器产生的气雾云进行表征。该适配器有一个预分离器，用于在气雾云暴露于激光束之前将大颗粒（即载体晶体）从气雾云中分离出来。它还有一个细颗粒收集器，用于在激光衍射测量粒径后通过化学检测方法测量细颗粒的排放质量分数。该封闭系统能够控制通过气雾剂发生器的气流，并且所有测试条件，包括环境温度和相对湿度，都会自动记录。逆流可将颗粒沉积在激光束的两个窗口上的情况降至最低，从而无需清洁这些窗口就能进行连续测量。该适配器已成功用于雾化器、MDI和DPI的测试。在对十种雾化器的比较研究中发现，当这些设备在制造商推荐的条件下使用时，对于相同的10%硫酸妥布霉素水溶液（体积中值直径范围为1.25至3.25微米），它们产生的气雾云的液滴大小（分布）有很大差异。在雾化过程中，旁流式（使用PortaNeb压缩机）产生的液滴大小分布非常稳定，直到设备干运行。使用该适配器对含有球形颗粒剂型药物（例如阿斯利康都保）的DPI进行比较测试快速且简单。而且，含有较大载体材料的制剂也能成功测量。对于含有16.7%乳糖（粒径106 - 150微米）的硫酸黏菌素制剂以及含有Pharmatose 325和150 M载体混合物的布地奈德制剂，带有载体保留装置（用作预分离器）的测试吸入器的崩解效率都能相当准确地测量。因此，可以得出结论，借助这种特殊的适配器，激光衍射可能是用于吸入器比较评估、设备开发、粉末制剂和质量控制的有价值工具。与级联冲击器分析相比，激光衍射速度要快得多。此外，还能获得有关气雾云更详细且不同的信息。
