Hoppentocht M, Hoste C, Hagedoorn P, Frijlink H W, de Boer A H
Department of Pharmaceutical Technology and Biopharmacy, University of Groningen, Groningen, The Netherlands.
Laboratory of Pharmaceutical Technology, University of Ghent, Ghent, Belgium.
Eur J Pharm Biopharm. 2014 Sep;88(1):153-9. doi: 10.1016/j.ejpb.2014.06.014. Epub 2014 Jun 30.
Dry powder formulations for inhalation have to be screened in animal studies for therapeutic efficacy and safety aspects and both are significantly affected by the dose and the particle size distribution (PSD) of the aerosol that is given. One of the most frequently used apparatus for pulmonary delivery of dry powder formulations in mice studies is the PennCentury DP-4M Dry Powder Insufflator. To make researchers of future preclinical animal studies with the DP-4M insufflator aware of the pitfalls regarding the conclusions to be drawn from their data, we investigated the dispersion behaviour by the DP-4M insufflator using two to three different powder preparation techniques for four different compounds. The primary PSDs of the different formulations were determined in duplicate by laser diffraction analysis. To measure the PSDs of the aerosols obtained with the DP-4M insufflator, the same diffractometer was used in combination with an in-house constructed adapter for the insufflator. The dispersion efficiency and delivered dose were highly affected by the amount of air available for dispersion; the 200 μL of air recommended for the type of insufflator used was insufficient for adequate dispersion. In contrast, the weighed dose did not have a profound effect on the dispersion behaviour and the delivered dose of the DP-4M insufflator. Also the physico-chemical powder properties and the applied particle preparation technique influenced the amount and PSD of the delivered aerosol only to a limited extend, with a few exceptions. We advise researchers to investigate the dispersion efficiency and delivered dose from the DP-4M insufflator with the formulation under investigation prior to in vivo studies and it may be necessary to optimise the formulation for administration to mice.
用于吸入的干粉制剂必须在动物研究中进行治疗效果和安全性方面的筛选，而这两者都会受到所给予气雾剂的剂量和粒径分布（PSD）的显著影响。在小鼠研究中，用于肺部递送干粉制剂的最常用仪器之一是PennCentury DP - 4M干粉吸入器。为了让未来使用DP - 4M吸入器进行临床前动物研究的研究人员意识到从其数据得出结论时存在的陷阱，我们使用两种到三种不同的粉末制备技术，对四种不同化合物研究了DP - 4M吸入器的分散行为。通过激光衍射分析对不同制剂的初级PSD进行了一式两份的测定。为了测量用DP - 4M吸入器获得的气雾剂的PSD，使用同一台衍射仪并结合为该吸入器自制的适配器。分散效率和递送剂量受可用于分散的空气量的高度影响；所使用的吸入器类型推荐的200μL空气不足以实现充分分散。相比之下，称重剂量对DP - 4M吸入器的分散行为和递送剂量没有深远影响。物理化学粉末性质和所应用的颗粒制备技术也仅在有限程度上影响递送气雾剂的量和PSD，但有一些例外情况。我们建议研究人员在体内研究之前，用所研究的制剂研究DP - 4M吸入器的分散效率和递送剂量，并且可能有必要优化用于给小鼠给药的制剂。
