Sponsors may require a cocrystal screen for a number of reasons, or a combination of these:
• Dissolution rate/ solubility
There is strong theoretical basis for cocrystals possessing high dissolution rates in water, this is explained below. Strictly speaking solubility is measured at equilibrium with undissolved solid and is a fixed thermodynamic property. In practice, however formulation often uses non-equilibrium conditions and this gives a useful window of apparently higher solubility.
• Crystallinity
Cocrystals give access to a wide range of potentially crystalline forms and are especially favoured where the API is neutral or unstable to acid.
• Novelty
A new cocrystal form is patentable if it has some demonstrable advantage over the prior art and the inventor has a proven method of preparation, i.e. reduction to practice. It is therefore prudent to look for optimal solid forms that offer little scope for attack from competitors who may see an opportunity to exploit a flawed profile.
• Hydration issues
Where the API has high water affinity, consideration of the H-bond balance (donors v. acceptors) can suggest classes of coformer that satisfy the H-bond potential of the API and hence give stable cocrystals.
• Other processability
This can include issues in large scale synthesis such as slow filtration, and further downstream processes such as compressibility etc.
• Stability
Compounds that are unstable to acids strong enough to make salts may be suitable candidates for cocrystal formation.
