Seeding heel recycle

The most effective seeding is achieved in semicontinuous and continuous crystallizations by the nature of the operations themselves, in which the seed is always present and in large quantity. Although common in large industrial operations, these techniques have found more limited application in the pharmaceutical industry. Exceptions to this are detailed in Examples 7-6 and 11-6, on the continuous resolution of optical isomers in fluid bed crystal-fizers, and in Example 10-1, which presents a semicontinuous method of utilizing seed heel recycle in reactive crystallization to achieve primarily growth. 

Seed from the previous batch—added separately or as heel recycle effective if the physical and chemical attributes and stability remain satisfactorily constant or can be normalized by intermediate treatment... 

Seed from heel recycling with wet milling to control the mean particle size and PSD one of the most effective seeding procedures when applicable (see Example 10-1)... 

Seeding with dry powder seed through a vessel head nozzle, while widely practiced in the past, is now limited because of safety and exposure considerations. Slurry seed additions by pump or from seed tanks are preferred and are superior to powder addition for the reasons discussed above. The advantages of retaining the seed in the system, as utilized in continuous operation or in heel recycling are also indicated above. 

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