Screening of Pharmaceutical Co-Crystals in Solution Crystallization

In recent years co-crystal formation has emerged as a viable strategy towards improving the solubility and bioavailability of poorly soluble drugs. The solution crystallization was used to produce co-crystals of active pharmaceutical ingredients (APIs): clopidogrel hydrogen sulfate, aripiprazole, bicalutamide, etc.. Co-crystals using the pharmaceutically acceptable co-former were produced from solution through evaporation and cooling crystallization methods.

Three unique solid phase utilizing six co-formers were generated in the screening experiments. The corresponding co-crystalline phases were screened by in-situ measurement and characterized by differential scanning calorimetry (DSC) and powder X-ray diffraction (PXRD). Phase solubility diagrams are used to illustrate how saturation of the reactants leads to supersaturation of the co-crystal. Kinetic and thermodynamic studies on co-crystal formation were carried out.