Experimental cocrystal screening and solution based scale-up cocrystallization methods

Area of Science:

• Pharmaceutical Science
• Materials Science
• Chemical Engineering

Background:

• Cocrystals, defined as single-phase crystalline materials of two or more compounds, are gaining traction in drug development.
• Pharmaceutical cocrystals, involving an active pharmaceutical ingredient (API), offer a strategy to improve physicochemical and biopharmaceutical properties.
• Traditional screening methods rely on crystal engineering principles and solution-based crystallization, similar to polymorph and salt screening.

Purpose of the Study:

• To provide an overview of solid form screening techniques in drug development, focusing on cocrystal screening.
• To highlight advancements in understanding cocrystal phase behavior and its application in screening and scale-up.
• To review current research on solution-based and continuous crystallization methods for cocrystal production.

Main Methods:

• Review of literature on solid form screening techniques, with emphasis on cocrystal methodologies.
• Analysis of advancements in cocrystal phase behavior understanding and application of phase diagrams.
• Examination of state-of-the-art research in solution-based and continuous cocrystallization processes.

Main Results:

• The study reviews commonly employed solid form screening techniques and emphasizes cocrystal screening methodologies.
• It presents the latest developments in understanding and utilizing cocrystal phase diagrams for screening and scale-up.
• The review covers solution-based scale-up processes and recent continuous crystallization methods for cocrystals.

Conclusions:

• Cocrystal screening and scale-up methods are evolving with a deeper understanding of phase behavior.
• Rational experimental design and the use of phase diagrams are crucial for efficient cocrystal development.
• Both solution-based and continuous crystallization techniques are important for the scale-up of pharmaceutical cocrystals.