|dc.description.abstract||Continuous manufacturing (CM) in pharmaceutical industry involves work up, reaction,
crystallisation, filtration and further downstream processes. This PhD work is focused
on work up processes, in particular how to feed solids directly into a liquid stream. This
requires the understanding of dissolution kinetics as well as parameters affecting kinetics.
A Twin Screw Extruder (TSE) is used in this PhD project as a tool for continuous
dissolution; acetylsalicylic acid, benzoic acid, nicotinic acid and paracetamol of different
sizes are the test candidates.
It was found that faster dissolution rates were achieved within the TSE in comparison
to a stirred tank vessel as a result of shorter mass transfer times and more aggressive
mixing. Solubility was identified as the major parameter affecting dissolution rates,
temperature is the second contributing factor, while mixing has less effect. Material with
the smallest particle size has the fastest dissolution rate, however is difficult to dispense
in bulk due to poor flow properties. The TSE enables the decoupling of liquid from the
solid feed, thus eliminating any potential fouled solid feeding; allows solution consistency
at the exit of the TSE even feeding at low solid feed rates, e.g. 2 g min-1.
Variable solid and liquid flow rates in the TSE are tested, full dissolution of powder
paracetamol is attained within the residence time of the TSE, while full dissolution of
benzoic acid and acetylsalicylic acid is achievable by having higher barrel temperature.
nicotinic acid exits the TSE as a consistent slurry. Dissolution kinetics for the four APIs
(Active Pharmaceutical Ingredients) are established. This work also demonstrates that
the TSE is a novel and valid tool for work up, allowing the controlled and synchronised
input flows, together with intense mixing, to deliver a dissolved solution within the
residence time of the barrel.||en