Applications of capsule dosing techniques for use in dry powder inhalers

Abstract

Dry powder inhaler (DPI) devices that utilize two-piece capsules as the dose-holding system can require specialized dosing equipment to fill the capsules. Such products are known as ‘premetered’ because they contain previously measured doses in a dose carrier (the capsule). The capsule is either inserted into the device during manufacture or by the patient prior to use. The dose is inhaled directly from the device/premetered unit by the patient. Regardless of DPI design, the most crucial attributes are the reproducibility of the discharged dose and the particle size distribution of the drug within that dose. Filling inhalation powders into capsules often requires specialized equipment in order to handle the very low weights that are often contained in each dose. The equipment typically needs to incorporate in-process checks to confirm the filling process has been correctly performed, with the ability to reject any under- or over-filled capsules, in line with established quality criteria. In the majority of cases, such processing equipment is maintained in a temperature and humidity controlled environment to avoid moisture uptake and potential powder aggregation and, in particular, to ensure the powder is free flowing on introduction into the capsule. This ensures that the emitted dose is maximized and controlled according to industry guidelines and that the fine particle fraction provides an optimum clinical benefit. Several methods of dosing precise doses of powder into capsules are available and include dosator technology and tamp processes, as well as equipment that utilize the ‘pepper-shaker’ or ‘pepper-pot’ principle for the accurate dispensing of powders. This article reviews the suitability of each method with respect to dosing inhalation powder into capsules for use in DPI devices, and discusses why the pepper-pot principle could offer a number of clear benefits.