Commercialization of the Xalkori Pediatric Multiparticulate Product Using Quality-by-Design Principles.

A pediatric dosage form for crizotinib (Xalkori) was commercialized using quality-by-design principles in a material-sparing fashion. The dosage form consists of spherical multiparticulates (microspheres or pellets) that are coated and encapsulated in capsules for opening. The crizotinib (Xalkori)-coated pellet product is approved in the US for pediatric patients 1 year of age and older and young adults with relapsed or refractory, systemic anaplastic large cell lymphoma (ALCL) and unresectable, recurrent, or refractory inflammatory myofibroblastic tumor (IMT) that is ALK-positive.

Application of Online NIR Spectroscopy to Enhance Process Understanding and Enable In-process Control Testing of Secondary Drying Process for a Spray-dried Solid Dispersion Intermediate.

Near infrared spectroscopy (NIRS) was utilized to determine the endpoint of secondary drying process (post primary spray drying) of Spray-Dried Intermediates (SDI). In addition, NIR methods have been developed to quantify residual solvents (acetone and water), which are in-process controls (IPCs), and assay on the spray dried intermediate, thereby minimizing the need for off-line sample testing. NIRS calibration models were built with Partial Least Squares (PLS) regression for samples from several statistically designed experiments.

Combination of Colloidal Silicon Dioxide with Spray-Dried Solid Dispersion to Facilitate Discharge from an Agitated Dryer.

A feasibility evaluation of the addition of fumed silica (SiO) into an agitated dryer to aid spray-dried solid dispersion intermediate (SDSDi) flow during secondary drying and discharge is described. The quantity of SiO to enhance the flow character of SDSDi was assessed by measuring particle size distribution, bulk density, and flow-through-an-orifice. Results indicate that the addition of the SiO did not alter the drying kinetics and did not impact the bulk particle size distribution of the SDSDi.

Application of Online Near Infrared for Process Understanding of Spray-Drying Solution Preparation.

Solution preparation is the first unit operation of the manufacturing process for spray-dried solid dispersions. Visual inspection and offline high-performance liquid chromatography analysis are routinely used to assess the solution preparation end point as well as the final solution composition. However, the accuracy and appropriateness of these approaches are challenged by the scale of production and solvent evaporation during sample handling.