de Boer A H, Gjaltema D, Hagedoorn P, 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):219-31. doi: 10.1016/s0378-5173(02)00526-4.
Cascade impactor analysis is the standard technique for in vitro characterization of aerosol clouds generated by medical aerosol generators. One important reason for using this inertial separation principle is that drug fractions are classified into aerodynamic size ranges that are relevant to the deposition in the respiratory tract. Measurement of these fractions with chemical detection methods enables establishment of the particle size distribution of the drug in the presence of excipients. However, the technique is laborious and time consuming and most of the devices used for inhaler evaluation lack sufficient possibilities for automation. In addition to that, impactors often have to be operated under conditions for which they were not designed and calibrated. Particularly, flow rates through impactors are increased to values at which the flow through the nozzles is highly turbulent. This has an uncontrolled influence on the collection efficiencies and cut-off curves of these nozzles. Moreover, the cut-off value varies with the flow rate through an impactor nozzle. On the other hand, the high air flow resistances of most impactors are rather restricting to the attainable (fixed) inspiratory flow curves through these devices. Especially for breath actuated dry powder inhalers, higher flow rates and flow increase rates may be desirable than can be achieved in combination with a particular type of impactor. In this paper, the applicability of laser diffraction technology is evaluated as a very fast and highly reliable alternative for cascade impactor analysis. With this technique, aerodynamic diameters cannot be measured, but for comparative evaluation and development, comprising most in vitro applications, this is not necessary. Laser diffraction has excellent possibilities for automated recording of data and testing conditions, and the size classes are independent of the flow rate. Practical limitations can be overcome by using a special inhaler adapter which enables control of the inspiratory flow curve through the inhaler, analysis of the emitted fine particle mass fraction and pre-separation of large particles during testing of dry powder inhalers containing adhesive mixtures.
级联冲击器分析是用于对医用气溶胶发生器产生的气溶胶云进行体外表征的标准技术。采用这种惯性分离原理的一个重要原因是，药物组分被分类到与呼吸道沉积相关的空气动力学粒径范围内。用化学检测方法测量这些组分能够确定在辅料存在的情况下药物的粒度分布。然而，该技术既费力又耗时，而且大多数用于吸入器评估的设备缺乏足够的自动化可能性。除此之外，冲击器常常必须在其未设计和校准的条件下运行。特别是，通过冲击器的流速会增加到使通过喷嘴的流动处于高度湍流的数值。这对这些喷嘴的收集效率和截止曲线产生了无法控制的影响。此外，截止值会随通过冲击器喷嘴的流速而变化。另一方面，大多数冲击器的高气流阻力对通过这些设备可达到的（固定）吸气流量曲线有相当大的限制。特别是对于呼吸驱动的干粉吸入器，可能需要比与特定类型的冲击器组合所能实现的更高的流速和流速增加率。在本文中，评估了激光衍射技术作为级联冲击器分析的一种非常快速且高度可靠的替代方法的适用性。利用这种技术无法测量空气动力学直径，但对于包括大多数体外应用的比较评估和开发而言，这并非必要。激光衍射在自动记录数据和测试条件方面具有出色的可能性，并且粒径类别与流速无关。通过使用一种特殊的吸入器适配器可以克服实际限制，该适配器能够控制通过吸入器的吸气流量曲线、分析所释放的细颗粒质量分数以及在测试含有粘性混合物的干粉吸入器期间对大颗粒进行预分离。
