(116f) In-Situ Seed Generation with Wet Milling for Pharmaceutical Crystallization

A practical technique for generation of in-situ (wet) seed for pharmaceutical crystallization is successfully developed at Abbott Laboratories. Under controlled supersaturation and high mixing intensity environment, it was demonstrated for several pharmaceutical compounds and intermediates that very fine particles can be generated in-situ and used in the crystallization subsequently. This replaces the needs for the off-line seed preparation and simplifies various related issues such as storage stability of seed and analytical release. Supersaturation, mixing intensity and solvent composition were found to be variables and can be used to overcome oil/amorphous solid complications, and tune the crystal form and particle size. Laboratory and pilot plant results are presented to illustrate the utilization of this technique