Cocktail-Solvent Screening to Enhance Solubility, Increase Crystal Yield, and Induce Polymorphs

摘要

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 pharmaceuti-cals (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 enhance-