No-shaking and shake-fire delays affect respirable dose for suspension but not solution pMDIs

Abstract

It has long been accepted that suspension pressurized metered-dose inhalers (pMDIs) must be shaken if a correct dose is to be delivered, if not, it will usually be higher than the label claim. The purpose of this work was to investigate the influence of the device being unshaken, shaken and after a period of delay in pMDI actuation on the Fine Particle Mass (<5 µm), Extra Fine Particle Mass (<2 µm) and MMAD. Solution and suspension commercial pMDIs containing one, two or three components were used in the study. Most of the suspension pMDIs produced variable amounts of respirable size drug following the shake-fire delays tested in terms of the label claim dose. The effect was even more critical if the inhaler was not shaken and the FPM was found to be between -82 % for Symbicort and 363 % for Ventolin compared with the control values. In the case of MMAD measurements, Seretide and Serzyl inhalers showed the largest change from around 3 µm to 4.2-5.1 µm when not shaken. Conversely, the FPM and MMAD for the solution aerosols remained unchanged whether or not they were shaken or when a progressive increase in the delay in actuation after shaking was employed.

Keywords: Adherence; Critical error; Device misusing; Device shaking; Extra-fine dose; Metered dose inhaler.