ABSTRACT
The objective of this study was to evaluate the effect of valve silicone on the delivered particle size distribution of a suspension metered dose inhaler (MDI). Valves were manufactured with distinct levels of silicone, which could be differentiated with Fourier transform infrared spectroscopy (FT-IR). The amount of silicone in the valve was proportional to the amount of silicone that entered the formulation and the subsequent decrease in fine particle fraction (FPF) of the active pharmaceutical ingredient (API) measured by Andersen cascade impaction. The effect of silicone content was not linear as even small amounts of silicone made a significant contribution to particle size coarsening. This coarsening was also a function of storage time and temperature. Accelerated stability conditions greatly increased coarsening kinetics as 1 month at 40 degrees C and 75% RH induced significantly more coarsening than 12 months at room temperature. Field emission scanning electron micrograph images suggest that the primary mechanism of particle size change may be aggregation as particle clusters were seen. This study indicates that silicone can be a critical process parameter for particle size distribution of a suspension MDI product. Thus, the amount of silicone in the valves needs to be minimized and controlled.
