Harvesting Potential Dissolution Advantages of Soluble Cocrystals by Depressing Precipitation Using the Common Coformer Effect

A highly soluble cocrystal of a poorly soluble drug has the potential to improve the dissolution rate and bioavailability. Reaping the potential dissolution advantage of soluble cocrystals is challenged by the precipitation of the parent drug during dissolution. Using the carbamazepine-nicotinamide cocrystal, we show that the use of excess coformer can be an effective strategy for eliminating precipitation during dissolution by taking advantage of the "common coformer effect". When excess coformer is present, the solubility of the cocrystal is depressed, which leads to a lower degree of supersaturation. At an appropriate level, precipitation can be prevented and improved dissolution is realized.