Summary

Introduction: Suspensions are heterogeneous systems consisting of solid particles dispersed in a liquid continuous phase. A homogenous dispersion of Active Pharmaceutical Ingredients APIs is critical for pressurized metered dose inhalers pMDIs suspensions to enable delivery of consistent delivered drug doses. Non-uniform dispersion of Active Pharmaceutical Ingredients APIs in suspension could occur in pressurized metered dose inhalers pMDIs due to inadequate homogenisation, and mixing during bulk suspension manufacture prior to canister filling, or too rapid flocculation or agglomeration of the formulation within the filled canister leading to sedimentation or creaming, which if occurring too rapidly between the shake and fire cycle of the patient or laboratory analyst, may lead to variability in delivered dose of Active Pharmaceutical Ingredients APIs through container life. Materials and Methods: Visual observation, as well as dynamic image analysis, have been used to monitor sedimentation, flocculation, or creaming patterns of different Active Pharmaceutical Ingredients APIs with excipients in different pressurized metered dose inhalers pMDI suspension formulations over time. Results and Discussion: The API(s) suspended in the propellant could sediment or cream depending on their relative densities. This behaviour is modified using excipients such as dispersing or suspending agents (polyethylene glycol or polyvinylpyrrolidone), with the aim to form a homogenous suspension for ensuring consistency in filled canister assays, and delivered dose uniformity. Those excipients adjust the overall density of the propellant formulation to more closely match the density of the Active Pharmaceutical Ingredient API. The impact of the dispersing or suspending agents is monitored by dynamic image analysis through time. Conclusion: Dynamic image analysis could be a valuable pre-formulation tool to predict the suspension stability of pressurized metered dose inhalers pMDIs.

Key Message

The behaviour of different APIs suspended in propellant systems with dispersing or suspending agents as excipients have been investigated using dynamic image analysis. This technology could act as a valuable tool to predict the physical stability of Hydrofluoroalkane HFA based pressurized metered dose inhalers pMDIs suspensions.