Delivery of Dry Powders to the Lungs: Influence of Particle Attributes from a Biological and Technological Point of View

Dry powder inhalers are medical devices used to deliver powder formulations of active pharmaceutical ingredients via oral inhalation to the lungs. Drug particles, from a biological perspective, should reach the targeted site, dissolve and permeate through the epithelial cell layer in order to deliver a therapeutic effect. However, drug particle attributes that lead to a biological activity are not always consistent with the technical requirements necessary for formulation design. For example, small cohesive drug particles may interact with neighbouring particles, resulting in large aggregates or even agglomerates that show poor flowability, solubility and permeability. To circumvent these hurdles, most dry powder inhalers currently on the market are carrier-based formulations. These formulations comprise drug particles, which are blended with larger carrier particles that need to detach again from the carrier during inhalation. Apart from blending process parameters, inhaler type used and patient's inspiratory force, drug detachment strongly depends on the drug and carrier particle characteristics such as size, shape, solid-state and morphology as well as their interdependency. This review discusses critical particle characteristics. We consider size of the drug (1-5 µm in order to reach the lung), solid-state (crystalline to guarantee stability versus amorphous to improve dissolution), shape (spherical drug particles to avoid macrophage clearance) and surface morphology of the carrier (regular shaped smooth or nano-rough carrier surfaces for improved drug detachment.) that need to be considered in dry powder inhaler development taking into account the lung as biological barrier.