Electrostatic charge characteristics of aerosols produced from metered dose inhalers.

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. (c) 2005 Wiley-Liss, Inc.