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The study focuses on the selection of container closure system for metered dose inhalers (pMDIs), a critical factor in developing and manufacturing a successful pMDI. The metering valve plays a fundamental role in ensuring delivered dose uniformity and protecting the structural integrity of pMDIs. The elastomer seal secures the valve onto the canister, which then hermetically isolates the system to ensure the pressure of the propellant is maintained. However, the crimp around the valve and canister is a source for water ingression into the drug product. In early development, selecting the right valve configuration is crucial to streamline the development program thereafter. The study evaluates 12 different valve configurations prepared containing a Fluticasone Propionate/Salmeterol Xinafoate 50/25 µg formulation. The study focused on demonstrating how two weeks of storage at an extreme stress condition (50 °C/75% RH) may be used to give indications of stability issues or preferential configurations, for a product. The results collected during this shortened stability study showed how extreme storage conditions (50 °C/75% RH) can be employed in order to predict product performance under ‘stressed conditions’, shorten the time for accelerated stability study from three months to two weeks. The use of this extreme storage condition in early development DoE studies would allow scientists to evaluate several valve/formulation combinations in a shortened timeframe and to select the best performing formulation and pMDI valve combinations more rapidly, either increasing the amount of variants to be tested early on, or increasing the speed/decreasing costs associated with a development program.
