Summary

Industry standard blending technologies, such as high shear mixers, do not adequately deagglomerate and disperse active pharmaceutical ingredient (API) particles at concentrations greater than 5%^w/_w so traditional carrier-based DPI systems are dose limited. It is thought that the challenge of developing a ‘high dose’ dry powder inhaler (DPI) formulation routinely requires the application of advanced manufacturing techniques such as spray drying to formulate powder blends. Unfortunately, such technologies often require that the API be subjected to less than ideal processing conditions and are disproportionately expensive to implement. A relatively new and benign dry powder blending technology has been employed in this work to attempt to extend the dosing range of traditional DPIs more simply. At the heart of this technology, individual particles are dispersed by centrifugal force and fluidised by an air-blade which does not damage the input materials. A model API, micronised fluticasone propionate (FP), was processed with inhalation grade lactose at concentrations of up to 25%^w/_w. At all concentrations studied, the new technique fully removed all agglomerates of the API. At FP concentrations above 5%^w/w, multilayers of fine particles were formed at the surface of the carrier particles. At all concentrations the formulations were found to produce homogeneous powder blends with excellent content uniformity, more than adequate for requirements of a high dose DPI formulation. Furthermore, the aerodynamic particle size distributions determined from each of the blends became increasingly fine as the FP concentration was increased. Scanning electron micrographs showed that multilayer structures formed at high concentration on the lactose surface have an open porous nature. It is reasonable to hypothesise that it is the nature of the structure of the surface coating that determines the respirable dose performance of the blend.

Key Message

A novel dry particle coating technology employing fluidisation produces high dose DPI formulations containing up to 25%^w/w API with a lactose carrier. An open porous coating of API on the lactose carrier created by application of the technology provides a homogeneous blend and facilitates aerosolisation of high therapeutic doses of API previously out of the range of conventional DPI formulations.