Co-crystal Screening

Sonication is also another method of generating co-crystals. It is applied to a solution or suspension. Although this technique is little used in co-crystal screening, a recent study has shown that pure co-crystals could be obtained using ultrasound assisted solution co-crystallization, where conventional solution crystallization failed. he use of melt crystallization methods have also been reported as efficient co-crystal screening methodologies. These techniques include thermal microscopy and differential scanning calorimetry methods.  

Horst et recently developed an interesting co-crystal screening 

Type of Solvent Chemical Species Low Boiling Point High Boiling Point 

Protic-polar Alcohol/Water Methanol Ethanol Hexane, butane Benzyl alcohol 

Aprotic-polar Ketone Acetone Methyl isobutyl ketone 

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G.G.Z. Zhang, R.F. Henry, T.B. Borchardt, X. Lou, Efficient co-crystal screening using solution-mediated phase transformation, J. Pharm. Sci. 96 (2007) 990-995. 

However, grinding in the presence of a small amount of a liquid phase (liquid-assisted grinding or LAG) was found to be highly efficient for the synthesis of co-crystals, resulting in rapid and quantitative formation of cocrystals, typically within 20 minutes. A suitable illustration of the greater efficiency of LAG for co-crystal screening is the proof-of-principle study of the... 

Table 5.5 Results of co-crystal screening involving the four model steroid ...

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... 

Phase diagrams are a powerful and intuitive tool for planning co-crystal screenings and crystallization optimizations. 

Table 2 Co-crystal screen of iso-nicotinamide and carboxylic acids...

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