Summary

Various methods of analyzing the behavior of the suspended particles in pressurized metered dose inhalers (pMDIs) using backscattering have been reported providing semi-quantitative information which can be useful in characterizing and selecting a formulation. However, those techniques have a high cost and are not intuitive in defining the initial and ending points of this dynamic phenomenon. Therefore, a reliable screening technique is required to study the impact of formulation on the behavior of the suspended particles. In this study, a novel shadow motion analysis (SMA) method is described, proving to be highly reproducible, relatively inexpensive, and a non-user dependent alternative capable of analyzing the stability of low density pMDI cosuspension formulations. The SMA method was used to collect images of the creaming process inside of a pMDI glass canister. Samples were exposed to a LED source of light, generating a shadow of the suspended particles which was captured by a monochromatic camera. A correlation between the area of the shadow by time was studied to create the creaming profile of the low-density cosuspension system.  Formulations containing a cosuspension of a micronized drug with spray-dried lipid particles were evaluated. The obtained creaming profiles were highly reproducible, and the technique was capable of differentiating between formulations of different drug concentrations. Additionally, it was shown that the creaming process is retarded when a high concentration of micronized drug was incorporated in the co-suspension.

Key Message

SMA has proven to be a reproducible method capable of differentiating formulations at relatively low cost compare to other alternatives. Data was fitted to a nonlinear, four-parameter logistic model to determine the decay rate of the creaming process.