Design strategies for solution-based metered dose inhalers

In a suspension MDI, the active pharmaceutical ingredient (API) is suspended in the delivered droplets, so there is not necessarily a direct link between droplet size and the size of the delivered API particles. In contrast, in solution MDIs, the API is completely and homogenously dissolved within the delivered droplets. This makes drug delivery a more predictable process and underpins the highly consistent dosing that such products deliver during their lifetime.

In the 1990s, the phasing out of chlorofluorcarbons (CFCs) as propellants in MDIs and their replacement by hydrofluoroalkanes (HFAs) led to a resurgence of interest in solution-based MDIs, and the associated growth of the knowledge base for this technology. As a result, we now have semi-empirical design equations for ethanol-HFA-based MDIs that enable performance matching and/or the reliable and rapid development of new products with well-defined performance characteristics. For solution-based MDIs, these include delivery efficiency, which is quantified via the metrics of fine particle fraction (FPF) and/or fine particle dose (FPD), and aerodynamic particle size distribution (APSD).

In this article, we examine the properties that influence MDI performance and the empirical formulae that allow the efficient manipulation of device geometry and formulation composition to meet defined drug delivery targets. The application of these relationships is illustrated via example data for ipratropium bromide (IpBr) formulations. The ability to predict and regulate performance substantially eases the development of solution MDIs for specific illnesses and, at the same time, focuses attention on strategies to advance the technology to further enhance clinical outcomes by, for example, improving patient acceptance and comfort.

Developing solution MDIs: a step-by-step approach