Kwok Philip Chi Lip, Glover William, Chan Hak-Kim
Faculty of Pharmacy, University of Sydney, Sydney, NSW 2006, Australia.
J Pharm Sci. 2005 Dec;94(12):2789-99. doi: 10.1002/jps.20395.
The electrostatic charge properties of aerosols produced by commercial metered dose inhalers (MDIs), including Ventolin, QVAR, Flixotide, Intal Forte, and Tilade were studied using a modified 13-stage electrical low pressure impactor (ELPI) with aerodynamic diameter cutoff ranging from 0.028 to 10.07 microm. All the stages are electrically insulated from each other with the last 12 stages connected individually to electrometers with sensitivity at femtoampere levels. Aerosol particles deposited on the impactor stages according to their aerodynamic diameters and their charges were measured by the electrometers. The deposited drug mass was assayed chemically using HPLC. The results show that particles of bipolar charge distribution were produced reproducibly from Intal Forte, Tilade, and Flixotide. In contrast, those from Ventolin and QVAR displayed charge variation, depending on the time lapse between actuations. This suggests that charge relaxation may influence the charging of these two MDIs. Mass distributions were reproducible for all MDIs except for Ventolin, the first puff from which was always the highest in dose. The different charge characteristics of the MDIs could be attributed to differences in the drug and formulation as well as valve materials. In general, submicron particles showed a larger variation in the charge-to-mass ratio (q/m). This indicated charge contribution by propellant/excipients (which produce submicron particles) rather than the drug itself. The calculated number of elementary charges per drug particle of size <or= 6.06 microm ranged from zero to several ten thousands. The charge level is sufficiently high to have a potential effect on the deposition of the inhaled particles in the respiratory tract. In conclusion, the ELPI provided more detailed charge information about the MDI aerosol particles. Different aerosol charge profiles were shown by commercial MDIs, and the results can be explained by variation in the drug, formulation and the MDI materials. The results may have practical significance on lung deposition of MDI aerosols and regulatory aspects of generic aerosol products.
使用一种改良的13级低压电冲击器（ELPI）研究了包括万托林、信必可都保、辅舒酮、强的松龙色甘酸钠气雾剂和噻乐米克在内的商用定量吸入器（MDIs）产生的气溶胶的静电荷特性，该冲击器的空气动力学直径截止范围为0.028至10.07微米。所有级彼此电绝缘，最后12级分别连接到灵敏度为飞安级的静电计。根据气溶胶颗粒的空气动力学直径，沉积在冲击器级上的颗粒及其电荷由静电计测量。沉积的药物质量通过高效液相色谱法进行化学分析。结果表明，强的松龙色甘酸钠气雾剂、噻乐米克和辅舒酮可重复性地产生双极电荷分布的颗粒。相比之下，万托林和信必可都保产生的颗粒电荷存在变化，这取决于两次启动之间的时间间隔。这表明电荷弛豫可能会影响这两种MDIs的充电。除万托林外，所有MDIs的质量分布都是可重复的，万托林的第一喷剂量总是最高的。MDIs不同的电荷特性可归因于药物、制剂以及阀门材料的差异。一般来说，亚微米颗粒的电荷质量比（q/m）变化较大。这表明是推进剂/赋形剂（产生亚微米颗粒）而非药物本身对电荷有贡献。计算得出尺寸≤6.06微米的每个药物颗粒的基本电荷数从零到数万不等。电荷水平足够高，可能会对吸入颗粒在呼吸道中的沉积产生潜在影响。总之，ELPI提供了有关MDI气溶胶颗粒更详细的电荷信息。商用MDIs显示出不同的气溶胶电荷分布，其结果可以通过药物、制剂和MDI材料的变化来解释。这些结果可能对MDI气溶胶在肺部的沉积以及通用气溶胶产品的监管方面具有实际意义。
