High throughput crystallization

Zhang, Z., Sauter, N. K., van den Bedem, H., SneU, G. and Deacon, A. M. (2006). Automated diffraction image analysis and spot searching for high-throughput crystal screening. /. Appl. Crystallogr. 39,112-119. 

Morissette SL, Soukasene S, Levinson D, Cima MJ, Almarsson O. Elucidation of crystal form diversity of the HIV protease inhibitor ritonavir by high-throughput crystallization. Proc Natl Acad Sci 2003 100(5) 2180-2184. 

Morisette SL, Almarsson O, Peterson ML, Remenar JF, Read MJ, Lemmo AV, Ellis S, Cima MJ, Gamer CR. 2004. High-throughput crystallization polymorphs, salts, co-crystals and solvates of pharmaceutical solids. Adv. Dmg Deliv. Rev. 56 275-300. 

To date robotic automation has been the dominant strategy both for miniaturizing standard crystallization protocols and for fostering high-throughput crystallization [11, 12]. This allows more trials to be conducted with a given sample volume. 

High-throughput crystallization polymorphs, salts, co-crystals 75. and solvates of pharmaceutical solids. Adv. Drug Del. Rev. 

Ideally, all in vivo data would be obtained for each compound s most stable polymorph, but in the real world medicinal chemists rarely make them and analytical chemists are unlikely to run slow, labor-intensive solubility experiments on the amorphous compounds and metastable polymorphs that they do make. Kinetic solubility measurements run in HT mode coupled with equilibrium solubility determinations for only a few compounds are the best that one can expect right now. The use of high-throughput crystallization and formulation techniques early on in drug discovery has been suggested, but not, so far, widely adopted. 

J. Remenar, J. MacPhee, B. Larson, V. Tyagi, J. Ho, D. Mcllroy, M. Hickey, P. Shaw, and O. Almarsson, Salt selection and simultaneous polymorphism assessment via high-throughput crystallization the case of sertraline, Org. Process Res. Dev., 1, 990-996 (2003). 

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