Breakage Assessment of Lath-Like Crystals in a Novel Laboratory-Scale Agitated Filter Bed Dryer

Abstract

Agitated filter bed dryer is often the equipment of choice in the pharmaceutical industry for the isolation of potent active pharmaceutical ingredients (API) from the mother liquor and subsequent drying through intermittent agitation. The use of an impeller to promote homogeneous drying could lead to undesirable size reduction of the crystal product due to shear deformation induced by the impeller blades during agitation, potentially causing off-specification product and further downstream processing issues. An evaluation of the breakage propensity of crystals during the initial development stage is therefore critical. A new versatile scale-down agitated filter bed dryer (AFBD) has been developed for this purpose. Carbamazepine dihydrate crystals that are prone to breakage have been used as model particles. The extent of particle breakage as a function of impeller rotational speed, size of clearance between the impeller and containing walls and base, and solvent content has been evaluated. A transition of breakage behaviour is observed, where carbamazepine dihydrate crystals undergo fragmentation first along the crystallographic plane [00l]. As the crystals become smaller and more equant, the breakage pattern switches to chipping. Unbound solvent content has a strong influence on the breakage, as particles break more readily at high solvent contents. The laboratory-scale instrument developed here provides a tool for comparative assessment of the propensity of particle attrition under agitated filter bed drying conditions.

Crystal and Particle Engineering – An Indispensable Tool for Developing and Manufacturing Quality Pharmaceutical Products

“…Goh et al developed a new laboratory scale test rig to simulate agitated filter bed drying (AFBD) that could be used in a FT4 powder rheometer [17]. The intent was to capture the essential features of an industrial-scale agitated filter bed dryer, capable of filtration, programmable axial and radial mixing, temperature and humidity control, vacuum and nitrogen purge, impeller blade customization, and process monitoring via built-in sensors for torque, temperature, pressure, and humidity.…”