Particle engineered mannitol for carrier-based inhalation - A serious alternative?

In dry powder inhalation (DPI), larger carrier particles, typically lactose, are blended with micronised active pharmaceutical ingredient (API) particles to improve handling, processability and inhalable fraction. Alternative carrier materials were researched for years, but did not enter the market yet. In this study, a common lactose carrier for DPI formulations and a spray granulated mannitol carrier were compared to evaluate if the particle engineered mannitol can be considered a serious alternative. Blends with five different API concentrations (0.1 to 4%) were prepared with two APIs. Physical carrier and blend characterisation regarding particle size, morphology, density, shear cell testing and dosing behaviour were performed. Aerodynamic assessment was done using two different inhaler devices (one capsule-based inhaler and one reservoir-based inhaler). In addition, the influence of different flow rates was examined. Results indicated that uniform dosing in metered mass and delivered dose over this API concentration range was achieved due to good flowability of the blends. Furthermore, linear dose delivery could be seen over the added API concentrations. Impaction analysis showed that the respirable fractions of mannitol blends were comparable (for salbutamol sulphate blends) or higher (for budesonide blends) than with a standard lactose carrier.