This article is part of a special issue on Drug Delivery
Factors affecting dry-powder inhalers
However, powders do not always exhibit these ideal properties. More often, powders are susceptible to moisture which can lead to changes in surface morphology and/or aggregation. In addition, non-uniformity and concentration gradients can result from segregation within the powder bed. These and other factors must be effectively managed during the preparation of formulations and their filling into DPI devices, regardless of device format.
Device. The DPI device into which the formulation is filled can also affect the selection of filling method and equipment. The types of DPIs range from simplistic, low efficiency, passive devices to high(er) efficiency, active delivery devices in which the aerosolization process is driven by an external energy source. In terms of powder filling, the most relevant variables are the size, shape, and array of cavities into which the powder is to be deposited. Reservoir-based devices contain a relatively large powder hopper compared with devices designed to deliver pre-metered powder doses, typically in the 1–30 mg range, usually into either capsules or preformed blister cavities. In this context, the dispensing of powders in the fill weight range of 1–30 mg is defined as microdosing.
Cavity arrangement can affect productivity. For example, the unit operations required to fill and index a circular array of cavities in a disc might require more time than filling a blister strip that indexes linearly. To overcome such device complexities, unique and tailored filling solutions are beneficial.
Although in simple terms, the process of filling DPI products merely requires the reproducible dispensing of powder aliquots into a cavity, the microdosing of ordered mixtures containing irregularly shaped particles of different particle-size distributions and mixed surface morphology represents a significant technical challenge. The need for device-specific equipment for high-speed operations and consistent processing adds to this challenge.
The challenge, therefore, has been in the development or identification of fit-for-purpose, manual or semi-automated filling equipment with the capability and functionality to handle inhaled powders in support of early DPI development studies. Although commonly used for early feasibility studies, manual dispensing of single-digit milligram quantities of powder is extremely labor-intensive and requires great manual dexterity. The nature of such manual operations can result in significant fill-weight variability, thereby causing an unnecessary number of rejected doses. Manual operations for inhalation delivery systems also have the potential to cause the powder to compress or to compress in an inconsistent manner. Such factors can contribute to variable delivery from the DPI device causing variability in key product-performance measures such as delivered dose uniformity and fine-particle dose. Such variability can lead to poor decision-making on the part of the inhalation development scientist regarding the suitability of a formulation or product for further development.