Alisertib sodium, an investigational oral oncology drug, posed some challenges toward developing a robust and scalable drying process employing an agitated filter dryer that manifested themselves during the technical transfer to a new manufacturing site. The API studied was a monohydrate that was found to readily dehydrate and agglomerate, impacting both drug product (DP) manufacture and in vitro dissolution. A scale down agitated filter dryer was designed that was used to study the drying unit operation and identify key process parameters. Through a combination of lab-and pilot plant-scale experiments, suitable drying conditions were developed that minimized agglomeration, eliminated dehydration, and produced API that behaved acceptably in downstream DP manufacture.

The bulk mechanical properties of two different types of rootzone sands (round and angular) were measured using a cubical triaxial tester. T wo monosize sands (d 50 = 0:375 mm and 0.675 mm) and their 50:50 binary mixtures (d 50 = 0:500 mm) were studied. T he compression, shear, and failure responses of the above-mentioned six compositions were analyzed, compared, and modeled. T wo elastic parameters (bulk and shear moduli) and two elastoplastic parameters (swelling and consolidation indices) of the six sand compositions were also calculated and compared. T he angular sand was more compressible than round sand during isotropic compression. In addition, the angular sands tended to have lower initial bulk density and high porosity values. Among the three different size fractions, the 0.375 mm mixture was least compressible for both sand shapes. T he failure strength and shear modulus of the angular sand were higher than the round sands. In addition, due to their simplicity, phenomenologica l models were developed to predict the compression and shear behavior of the sands. T he prediction models were validated using subangular and subround sands. Average relative difference values were calculated to determine the effectiveness of the prediction models. T he mean average relative difference values for compression pro® les, i.e., volumetric stress vs. volumetric strain, were from 16% to 39%, except for the initial load-response portion ( < 1% volumetric strain). T he predictive models were effective in reproducing the 145 failure responses: at 17.2 kPa con® ning pressure, the mean of average relative difference was 23%; at 34.5 kPa, the mean difference was 24%.

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