Screening for cocrystallization tendency: the role of intermolecular interactions

Area of Science:

• Physical Chemistry
• Materials Science
• Pharmaceutical Science

Background:

• Pharmaceutical cocrystals offer advantages over traditional solid forms.
• Limited understanding of solution behavior hinders effective cocrystal screening.
• Crystal engineering focuses on design but less on solution phase dynamics.

Purpose of the Study:

• To investigate solution physical chemistry for pharmaceutical cocrystallization.
• To identify reliable methods for screening API-ligand pairs for cocrystal formation.
• To establish a link between solution interactions and cocrystal outcomes.

Main Methods:

• Utilized pulsed gradient spin-echo nuclear magnetic resonance (PGSE NMR) to measure long-time self-diffusivities.
• Characterized particle interactions in solutions of active pharmaceutical ingredients (APIs) and ligands.
• Analyzed self-diffusivity to infer heteromeric and homomeric attractions.

Main Results:

• For API-ligand pairs forming cocrystals, heteromeric attractions exceed homomeric attractions.
• Stronger API-ligand interactions indicate an energetically favorable state for cocrystal formation.
• Self-diffusivity measurements provide insights into molecular interactions in solution.

Conclusions:

• Pair contribution of self-diffusivity serves as a novel screening tool for cocrystal formation.
• Understanding solution-phase interactions is crucial for efficient cocrystal development.
• This approach facilitates the identification of promising API-ligand combinations for cocrystallization.