A shaking control space study for a Fluticasone/Salmeterol metered dose inhaler based on spray pattern analysis

D. Farina, D., Z. Pitluk, S. Pallas. Poster presented at AAPS Annual Meeting and Exposition 2013; 2013 Nov 10 – 14; San Antonio, TX.

INTRODUCTION:  The purpose of the study was to identify conditions where a stable spray pattern could be produced using pMDIs. We chose a QbD approach to determine the effects of shaking on spray pattern performance of a fluticasone/salmeterol MDI product and used the results to determine if an optimal shaking regime for the product exists within the product’s control space. Because there is no known spray pattern size associated with “good shaking”, a decrease in the variability of the spray patterns was used as the indication of a good shaking routine.

BACKGROUND: Determining and defining the proper shaking regime for suspension metered dose inhaler (“MDI”) products that allows the formulation to be properly mixed and deliver the correct dose is a difficult challenge for product developers. It is well known that the spray pattern areas will change as a device is fired through life if the device is not shaken properly or the canister/valve temperature is not allowed to recover (i.e. the device is not operating isothermally). The change in spray pattern area is a function of the ratio of the formulation to propellant which changes in an unshaken or non-isothermal device. In this study, we took advantage of Proveris’s automated shake and fire actuation technology for MDIs to explore a shaking control space for the product based on a Design of Experiments model. Identification of the proper shaking routine as evidenced by stable spray pattern areas through life would allow the application of the spray pattern test for fast screening of the correct formulation fill level.

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