Focusing on powder processing in dry powder inhalation product development, manufacturing and performance.

ABSTRACT

Dry powder inhalers (DPI) are well established products for the delivery of actives via the pulmonary route. Various DPI products are marketed or developed for the treatment of local lung diseases such as chronic obstructive pulmonary disease (COPD), asthma or cystic fibrosis as well as systemic diseases targeted through inhaled delivery (i.e. Diabetes Mellitus). One of the key prerequisites of DPI formulations is that the aerodynamic size of the drug particles needs to be below 5 µm to enter deeply into the respiratory tract. These inherently cohesive inhalable size particles are either formulated as adhesive mixture with coarse carrier particles like lactose called carrier-based DPI or are formulated as free-flowing carrier-free particles (e.g. soft agglomerates, large hollow particles). In either case, it is common practice that drug and/or excipient particles of DPI formulations are obtained by processing API and API/excipients. The DPI manufacturing process heavily involves several particle and powder technologies such as micronization of the API, dry blending, powder filling and other particle engineering processes such as spray drying, crystallization etc. In this context, it is essential to thoroughly understand the impact of powder/particle properties and processing on the quality and performance of the DPI formulations. This will enable prediction of the processability of the DPI formulations and controlling the manufacturing process so that meticulously designed formulations are able to be finally developed as the finished DPI dosage form. This article is intended to provide a concise account of various aspects of DPI powder processing, including the process understanding and material properties that are important to achieve the desired DPI product quality. Various endeavors of model informed formulation/process design and development for DPI powder and PAT enabled process monitoring and control are also discussed.