Modulating crystal polymorphism via membrane-regulated supersaturation: an experimental and molecular dynamics...

Area of Science:

• Chemical Engineering
• Materials Science
• Crystallization Science

Background:

• Crystal properties critically influence pharmaceutical and food product functionality.
• Controlling crystal size and polymorphs is vital for product performance and stability.
• Glycine crystallization is a model system for studying polymorph control.

Purpose of the Study:

• To investigate membrane-assisted antisolvent crystallization (MAAC) for regulating glycine supersaturation.
• To determine if MAAC can selectively control polymorph formation and crystal growth kinetics.
• To elucidate the role of ethanol diffusion in modulating molecular self-assembly pathways.

Main Methods:

• Implemented MAAC using polyvinylidene fluoride (PVDF) membranes for controlled ethanol diffusion during glycine crystallization.
• Analyzed crystal size and polymorphic distribution.
• Performed molecular dynamics (MD) simulations of glycine-water-ethanol systems at varying supersaturation levels to study aggregate formation and nucleation kinetics.

Main Results:

• MAAC successfully produced α-glycine with a narrow size distribution (mean 86 μm).
• MD simulations indicated cyclic glycine dimers favored α-glycine at lower supersaturation, while disordered aggregates favored β-glycine at higher supersaturation.
• Ethanol modulated hydrogen bonding and self-assembly, influencing polymorphic outcomes, and induction times decreased significantly with increasing supersaturation.

Conclusions:

• MAAC offers precise control over supersaturation profiles in crystallization.
• This method enables selective formation of desired glycine polymorphs, specifically α-glycine.
• MD simulations provide molecular-level insights into MAAC's mechanism for polymorph control.