(96a) Understanding the Role of Drying History on the Crystallisation of Dehydrating Lactose Particles

Spray drying is one of the most commonly used technology to produce powders from atomised droplets that undergo evaporation. Operating temperature is well established to be a crucial parameter in affecting the physio-chemistry of particles, notably on particle crystallinity which provides better stability than amorphous particles. Lactose is a common pharmaceutical excipient. Previous reports suggested the use of high inlet temperature, up to 210^oC to improve lactose crystallinity.^[1] However, there are reports claiming that lower inlet temperature at 170^oC is more inclined to lactose crystallisation.^[2] In both cases, detailed study on the drying history and the state of particle throughout the drying time frame have not been explored. Spray drying temperature can only be controlled at the inlet/outlet of spray dryer leading to a constraint in drying temperature variation. This research addresses the current limitation by introducing a modified spray dryer known as ‘narrow tube dryer’ which entails 12 narrow copper tubes with internal diameter of 1.7 cm. Heat is supplied through the walls of the narrow tube via convection. Each 50 cm tube is isolated, hence enabling the amount of heat supplied to be controlled independently leading to a unique drying profile. With the aid of 1 Dimensional modelling, crucial parameters such as drying temperature profile, particle temperature, moisture content and glass transition temperature can be predicted throughout the drying time frame. This research focus on evaluating the impact of different drying history on lactose crystallinity. Results suggest the existence of an ‘active region’, a state where molecular movement occurs, as one of the determining factors on lactose crystallinity. The active region can be delineate using the predicted T_p-T_g curves of each drying condition. Within the active region, crystallisation is believed to happen as re-arrangement of atoms and molecules ensues. Particle duration in the active region is crucial, with a longer period providing more time for crystallisation. Lower drying temperature resulted in a shorter particle duration in the active region, hence yielding particle with a lower degree of crystallinity. Though high drying temperature produced a shorter active region, it was found that a sudden drop in drying temperature could instigate crystallisation similar to the crystallisation phenomena occurred in mannitol.^[3] This newly developed narrow tube dryer is capable in unveiling the drying history of particle and provide a more comprehensive understanding on particle crystallinity as the information of the state of particle throughout the drying chamber was used to analyse the crystallisation phenomena in spray dried lactose.

Keyword: Crystallisation, Pharmaceutical Engineering & Drug Delivery, Particle Characterisation

1. Chiou, D., T.A.G. Langrish, and R. Braham, The effect of temperature on the crystallinity of lactose powders produced by spray drying. Journal of Food Engineering, 2008. 86(2): p. 288-293.

2. Das, D. and T.A.G. Langrish, Combined Crystallization and Drying in a Pilot-Scale Spray Dryer. Drying Technology, 2012. 30(9): p. 998-1007.

3. Littringer, E.M., R. Paus, A. Mescher, H. Schroettner, P. Walzel, and N.A. Urbanetz, The morphology of spray dried mannitol particles — The vital importance of droplet size. Powder Technology, 2013. 239: p. 162-174.