Hansen solubility parameter as a tool to predict cocrystal formation.

Area of Science:

• Materials Science
• Pharmaceutical Chemistry
• Crystallization Engineering

Background:

• Cocrystal formation is crucial for improving drug properties.
• Predicting cocrystal formation requires understanding drug-coformer interactions.
• Hansen solubility parameters (HSPs) offer a theoretical framework for predicting miscibility.

Purpose of the Study:

• To determine if Hansen solubility parameters (HSPs) can predict drug-coformer miscibility and guide cocrystal screening.
• To evaluate different HSPs-based approaches for miscibility prediction.
• To discover new cocrystal forms of indomethacin.

Main Methods:

• Calculated HSPs for indomethacin and over 30 coformers using the group contribution method.
• Predicted miscibility using three established HSPs difference calculation approaches.
• Experimentally verified miscibility and cocrystal formation using differential scanning calorimetry and liquid-assisted grinding.

Main Results:

• HSPs-based miscibility predictions showed high agreement with experimental findings, with only one exception.
• All tested theoretical approaches consistently predicted miscibility.
• All systems that successfully formed cocrystals were experimentally confirmed as miscible; two new indomethacin cocrystals were discovered.

Conclusions:

• Drug and coformer miscibility, as predicted by HSPs, is a strong indicator of cocrystal formation.
• HSPs-based miscibility prediction can effectively guide the selection of coformers, reducing extensive screening efforts.
• This method shows promise for streamlining cocrystal discovery and development.