Attrition and Phase Changes during Agitated Filter Bed Drying

Active pharmaceutical ingredients (API) and excipients are normally present in crystal form, obtained by crystallisation, followed by filtration and drying. Filter bed drying is the unit operation of choice in the pharmaceutical industry, where the crystal suspension is first filtered, washed and then dried. Heat is applied to the filtered bed of crystals and agitated to promote heat transfer, and homogeneous moisture and temperature distributions as the bed dries. The agitation induces shear stresses within the bed, which can cause undesirable particle attrition and polymorphic transformations.
This thesis mainly addresses the research conducted in understanding the polymorphic phase transformation of carbamazepine dihydrate crystals and their breakage behaviour during agitated filter bed drying process. The coupled effect of thermal and mechanical stresses is isolated and studied. The dehydration and rehydration of the model crystals due to thermal and relative humidity gradients are studied under well controlled environmental conditions. The ramping rate of humidity is found to have some interesting effect of the water sorption capacity of the crystals.
The presence of cleavage planes in the acicular crystals or carbamazepine are investigated and related to their breakage behaviour due to impact using a novel aerodynamic dispersion method. Using this new approach, the breakability index of carbamazepine dihydrate crystals is determined. A new agitated filter bed test rig is developed to study the effect of process parameters on the breakage behaviour of the crystals. The breakage data correlates well with the input energy supply to the particle bed through impeller blade rotation. Rocky software based on Discrete Element Method (DEM) is used to study the effect of particle shape on the particle dynamics as well as the stress and strain distributions in an agitated bed.