Design, synthesis and properties of pharmaceutical cocrystals

Cocrystals are “solids that are single phase crystalline materials made up of two or more  different molecular and/or ionic compounds generally in a stoichiometric ratio which are  neither solvates nor simple salts.” A primary reason for current interest in cocrystals is down to their ability to alter the physicochemical properties of active pharmaceutical ingredients (APIs) without chemical modification of the API. That approximately 70% of new APIs under development have issues relating to low solubility and/or low permeability, means that  cocrystals could overcome such issues and improve, for example, dissolution rate, stability and  bioavailability of APIs.

The development of crystal engineering principles has reached a level of maturity for certain  types of functional groups, in particular carboxylic acid and pyridine moieties. This is not the case, however, for several other functional groups commonly found in APIs. In this context, this work addresses an understudied class of ionic cocrystals containing pharmaceutically acceptable dihydrogen phosphate (DHP) anions and phosphoric acid (PA) molecules and reports on their amenability to crystal engineering. 

The synthesis of cocrystals, particularly at scale, is often more challenging than that of single-component crystals and can be problematic with respect to purity, crystallinity and yield. This work highlights efficient methods for preparing and screening cocrystals.  

Most nutraceuticals are abundantly available within the plant kingdom and are associated with many beneficial health effects. Unfortunately, many of these nutraceuticals suffer from low  aqueous solubility leading, in turn, to poor absorption in the body that hinders their clinical performance. Herein, this work demonstrates how cocrystals can be exploited to overcome  these issues and offer an opportunity to prepare solid forms of nutraceuticals suitable for use in drug products.