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

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.

Automated summary

Agitated filter bed dryer is commonly used in the pharmaceutical industry for the isolation and drying of potent active pharmaceutical ingredients. However, the use of an impeller for homogeneous drying can cause undesired size reduction of crystal products. To evaluate the breakage propensity of crystals, a new versatile scale-down agitated filter bed dryer has been developed.