Crystalline products are widely used in the pharmaceutical industry as active pharmaceutical ingredients (APIs). However, these products are often susceptible to mechanical damage during isolation and drying processes, such as agitated filter bed drying (AFBD). AFBD involves the use of an impeller to promote uniform drying of the wet cake by intermittent agitation. However, the impeller also induces shear deformation on the crystals, resulting in size reduction and attrition. This can adversely affect the product quality and performance, as well as increase the downstream processing costs.
Therefore, it is essential to assess the breakage propensity of crystals during the early stages of product development. In this study, a new versatile scale-down AFBD has been developed for this purpose. The instrument can simulate the drying conditions of a commercial-scale AFBD and measure the extent of particle breakage under different operating parameters. Carbamazepine dihydrate, a commonly used API that is known to be brittle, has been selected as a model material. The breakage behaviour of carbamazepine dihydrate crystals has been investigated as a function of impeller rotational speed, impeller-wall and impeller-base clearance, and solvent content. It has been observed that the breakage mechanism of carbamazepine dihydrate crystals changes with their morphology and size. Initially, the crystals undergo fragmentation along the crystallographic plane [00l]. As the crystals become smaller and more equant, the breakage mode switches to chipping. Moreover, the solvent content has a significant influence on the breakage propensity, as higher solvent contents facilitate particle breakage.
In this study, a new versatile scale-down AFBD has been developed for this purpose, based on the FT4 chassis, in collaboration with Freeman Technology. The scale-down AFBD provides a valuable tool for comparative evaluation of the breakage tendency of different crystalline products under AFBD conditions. It can help pharmaceutical scientists to optimize their drying processes and achieve high-quality products with minimal attrition
