Engineering Stable Spray-Dried Biologic Powder for Inhalation

Abstract

This chapter reviews recent developments in the engineering of spray dried biologic powder for inhalation, with a focus on theories and methods for developing dispersible powders with long-term ambient storage stability. The first section provides an overview of the applications and advantages of spray drying biologics. Subsequent sections present detailed descriptions of the various stages spray dried biologics for inhalation undergo during development, manufacturing, and delivery: purification and formulation, atomisation, solvent evaporation and particle formation, particle collection and analysis, aerosolisation, and lung deposition. The discussion of solvent evaporation and particle formation includes a review of particle engineering models for designing particles with desired characteristics such as surface enrichment, solid state, and aerodynamic diameter. Amorphous glass stabilisation theories and stability testing methods are then reviewed. Subsequently, a spray dryer process model is derived using a mass and energy balance to predict the outlet temperature and relative humidity for different process parameters. Using moisture uptake data, this process model is coupled to a non-equilibrium supplemented phase diagram derived using plasticisation data for a trehalose-water system. Use of the supplemented phase diagram allows for the design of biologic powder with long-term physical stability at ambient temperature storage without requiring many experiments.