Co-crystallizing agent

C.B. Aakeroy, D.J. Salmon, M.M. Smith, J. Desper, Cyanooximes as effective and selective co-crystallizing agents, CrystEngComm 11 (2009) 439-443. 

Three of the four polymorphic compounds examined in this study [107] readily form co-crystals e.g. 2-hexeneoic acid isonicotinamide, 2-amino-5-nitropyrimi-dine 2-amino-3-nitropyridine, and 3-dimethylaminobenzoic acid 4-chlorobenza-mide. The structural behavior of 1-3 supports the suggestion that polymorphs make good co-crystallizing agents (provided that solubility differences are not too large). However, no co-crystals with maleic hydrazide were obtained, despite the fact that it exists in three different polymorphs. 

Two graphical representations of the isothermal phase diagram of the ternary system including the API, the co-crystallizing agent and the solvent exist, with... 

These observations are explained by a less numerous population of CBZ crystals and a higher co-crystal primary nucleation frequency. In this situation the consumption of CBZ by the co-crystal growth was not balanced by the CBZ crystals dissolution. From a process point of view, the introduction of an important quantity of co-crystal agent brings a net gain of operating time due to a faster SMTP rate and an increased co-crystallization yield because of lower final co-crystal solubility. 

Process development requires knowledge of the thermodynamics and kinetics of the system. From the earlier stages of development, an efficient co-crystal screening is essential. Of course this screening consists of finding out whether a co-crystal can be formed with one co-crystallizing agent or another, but it must also be able to detect the different possible stoichiometries and different... 

A pharmaceutical co-crystal according to claim 1, wherein the co-crystal agent is selected from sorbic acid, tranj-2-hexenoic acid, tranj-3-hexenoic acid, tra .s-4-hexenoic acid, tra j-2-butenoic acid, iranj-2-pentenoic acid, traro-3-pentenoic acid, tra .s-2,4-pentadienoic acid. ... 

Since 1 and 2 display many chemical similarities, it is reasonable to ascribe the superiority of 2 as a co-crystallizing agent to flie increased strength of the O-H N... 

Do Polymorphic Compounds Make Good Co-crystal I izing Agents [107] ... 

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