Characterisation of droplet formation in spray drying of inhaled medicines
Typ
Examensarbete för masterexamen
Master's Thesis
Master's Thesis
Program
Innovative and sustainable chemical engineering (MPISC), MSc
Publicerad
2022
Författare
Pawse, Rohit
Modellbyggare
Tidskriftstitel
ISSN
Volymtitel
Utgivare
Sammanfattning
Spray-drying is an established method for manufacturing of inhaled medicines. It facilitates the
engineering of particles and control over various attributes of particle formation. An important step
in this process is spraying, which is used to atomise the solvent solution into fine droplets. These
atomised droplets are then dried in the presence of hot air to form particles. Spray dried particles
have specific requirements when it comes to solid particle size and therefore control over particle size
is one of the key factors necessary to the success of this technology. Spray formation and atomisation
are however not well understood phenomenon and strong links between droplet formation and
particle formation are found in theory. Hence, a good understanding of how droplet formation occurs
and can be controlled is essential for the successful engineering of spray-dried particles. In this thesis,
a Schlick 970 S4 nozzle was used to study the influence of composition on droplet size using
formulations with different compositions of surface-active excipients and Active Pharmaceutical
Ingredients (API). A Malvern Spraytec was used to determine the droplet size distribution at a selected
range of flow parameters and changes in atomisation characteristics were studied by comparing the
changes in droplet sizes for various formulations at the same flow parameters. The influence and
effect of process parameters mainly liquid and gas flowrates on droplet formation are also studied
and trends are plotted. It is found that gas flowrate is the primary parameter affecting the droplet
formation and limitations on using the gas flowrate to manipulate the droplet size are identified. The
main findings of this work indicate that the presence of surface-active excipients and API result in a
reduction of droplet size and in turn solid particle size. This finding is further strengthened by
correlating droplet size data with solid particle size data resulting in a good correlation for Dv50 and
Dv90 values. Change in compositions ultimately result in changes to the physical properties of the
solution namely, surface tension and viscosity. It is then explored how changes in surface tension and
viscosity lead to changes in droplet size and strong correlations are observed. These strong
correlations are then justified through mechanisms in theory and the cause effect relationship is
identified. An attempt is also made using a high-speed camera to identify breakup mechanisms for
use in future studies.
Beskrivning
Ämne/nyckelord
Atomization , Nozzles , Spray-Drying , Droplet Size Measurements