On the effects of blending, physicochemical properties, and their interactions on the performance of carrier-based dry powders for inhalation – a review

Abstract

Blending drug and carrier powders to produce homogeneous drug–carrier adhesive mixtures is a key step in the production of dry powder inhaler (DPI) formulations. Although the blending conditions can result in different conclusions or probably change the outcome of a study entirely if being selected differently, there is a scarcity of data on the influence of blending processes on the physicochemical properties of bulk powder formulations and the follow-on effects on DPI performance. This paper provides an overview of the interactions between variables related to blending conditions (e.g. blending equipment, time, speed and sequence as well as environmental humidity) and powder physicochemical properties (e.g. size distribution, shape distribution, density, anomeric composition, electrostatic charge, surface, and bulk properties), and their effects on the performance of adhesive mixtures for inhalation in terms of drug content homogeneity, drug–carrier adhesion, and drug aerosolisation behaviour. The relevance of carrier payload, batch size and segregation were also discussed. Challenges and future directions were identified. This review therefore contributes towards a better understanding of the blending process, powder physicochemical properties, and their interlinked effects on the fundamental understanding of adhesive mixtures for inhalation. The knowledge gained is essential to ensure optimum blending and thereby controlled functionality of DPIs.