Fluralaner Crystallization Process

Example 4

Fluralaner was added at a concentration of 100 mg/mL in IPA, with 60 kg added to 600 L of isopropanol. This composition was heated to 65° C. over 1 hour, and aged for one hour to ensure full dissolution. The solution was cooled over 20 minutes to 50° C. and seeded with 600 g of crystalline fluralaner seed, again with unmilled seed crystals having an d50 of approximately 10 μm. The batch was further cooled to 20° C. over two hours to establish the starting particles. The batch was heated to 54° C., at which point 120 L of the batch was removed and heated to an elevated temperature until fully dissolved (>65° C.). The removal rate and return rate to the crystallizer were set to approximately 4.4-4.8 L/min. The recycle loop continued for 2.75 hours, at which point the d50 particle size dimension is approximately 40 μm. The batch was aged at 54° C. for 6 hours to further relieve supersaturation, then cooled to 45° C. over 6 hours, and further cooled to 0° C. over 16 hours. See FIG. 12 for a schematic of the process equipment. The resultant slurry was filtered and dried to produce fluralaner particles. Agitation was limited during the filtration and drying. The material was delumped at low speed in a conical mill. The dried fluralaner particles were measured to determine the particle dimensions and mechanical resiliency. See FIG. 13 for the particle size distribution and mechanical resiliency. See FIG. 14 for an SEM image of the resulting particles.