Mechanistic understanding of spray dried active pharmaceutical ingredients (APIs)

Spray drying is a continuous process that is able to form particles of determinable properties from a liquid feed in a single step. The development process for a spray drying operation can be challenging and expensive due to the requirement for numerous, large scale experiments. This is particularly the case in the pharmaceutical industry where raw materials can be expensive. Single droplet drying is a smaller scale technique that may be able to improve the development process by reducing this requirement. This thesis uses three different single droplet drying techniques to investigate the drying behaviour of aqueous solutions of choline bitartrate. It is found that the same drying behaviour is observed across all the techniques, even though the initial droplet size varies by up to an order of magnitude. The suspended droplet drying process is accurately modelled using a shrinking-core model and it is found that after the surface of the choline bitartrate droplet becomes saturated, there is a significant reduction in the droplet water activity leading to a slow drying rate. This is linked to the formation of a surface layer identified in the single droplet experiments.
The droplet sizes produced by two atomisers (ultrasonic and two-fluid) are investigated and the impact of changing different parameters is assessed. The two-fluid results are fitted to an empirical correlation to allow for approximate droplet sizes to be specified during spray drying. The results show that typical droplet sizes are around 50 μm, which is significantly smaller than the droplets used during the suspended droplet drying (around 1500 μm). Despite of this, it is shown that the single droplet drying results are able to accurately account for the behaviours observed during spray drying for aqueous solutions of choline bitartrate and L-glutamic acid. This demonstrates single droplet dryings potential as a predictive technique that can inform on spray drying behaviour.