Jim Clay
Kindeva Drug Delivery Ltd, Loughborough, Leicestershire LE11 5SF, UK
Summary
The analytical methodology for uniformity of delivered dose (UoDD) and dose content uniformity (DCU) can be sensitive to user-operation variability associated with the shaking and actuation process of pressurised metered dose inhalers (pMDIs) [1]. With the transition to low Global Warming Potential (GWP) propellants, suspension formulations may behave differently with the new propellant compared to their more traditional propellant counterpart. The analytical method therefore may require tight control of these shaking and actuation parameters for the priming, dose collection and waste actuations. It is the parameters for priming and dose collection that have been assessed during this study, by use of automation.
All data were generated using HPLC-UV (High Performance Liquid Chromatography – Ultraviolet) detection methodology.
The data demonstrate that an ethanol free, HFA152a, sedimenting suspension formulation can be highly susceptible to user-operation variability associated with the shaking and actuation process of pMDIs. Delivered dose data can vary greatly if parameters are not controlled, with an increase in dose in excess of 250% of target observed, when parameters are varied by only 2 to 3 seconds.
Automated dose collection apparatus (e.g. Vertus® from Copley Scientific, Nottingham, UK) can be used to understand user-operation variability and to control and minimise the effect of these parameters during routine analysis.