Cocktail-Solvent Screening

Crystallization from solutions is not only an important step in the fabrication of various functional materials in biological systems, but also a key separation and purification process in the manufacture of many fine chemicals and specialty chemicals, especially pharmaceuticals (1, 2). Pharmaceutical crystallizations are often carried out in batches of organic solvents or mixtures of solvents through temperature cooling (3). Because of the excess properties (i.e., the difference between the real properties and the ideal properties) for a real solution, the solubility of an active pharmaceutical ingredient (API) in a solvent mixture is sometimes higher than its solubility in a single solvent as the activity coefficient decreases (4, 5). The solubility enhancement that the solvent mix offers can bring three main advantages to pharmaceutical batch crystallization:

* It replaces excellent but environmentally harmful solvents such as tetrahydrofuran (THF), N, N-dimethylformamide (DMF), and N, N-dimethylacetamide (DMA) with greener solvents such as alcohols, acetonitrile, and water
* It gives a higher crystal yield
* It increases the degree of supersaturation, thus allowing nucleation to be controlled by the lowest nucleation barrier so that the metastable, instead of the thermodynamically stable crystalline phase, is induced (6–8).