Nonmimetic Gels Direct Novel Crystallization Behavior of Lenalidomide

Area of Science:

• Solid-state chemistry
• Supramolecular chemistry
• Pharmaceutical crystallization

Background:

• Supramolecular gels enable distinct solid-state outcomes compared to solution crystallization.
• Tailoring gelator structure to mimic substrates can control crystallization.
• Non-mimetic gelators typically show no influence on crystallization outcomes.

Purpose of the Study:

• Investigate lenalidomide crystallization within mimetic and nonmimetic gels.
• Explore the role of gelator structure and gel environment in crystallization control.
• Compare gel-phase crystallization outcomes with traditional solution-phase methods.

Main Methods:

• Utilized supramolecular gels with mimetic and nonmimetic gelators.
• Performed crystallization experiments in cyclopentanone and ethanol gel phases.
• Analyzed solid-state outcomes using solution-state Nuclear Magnetic Resonance (NMR) studies.

Main Results:

• A novel cyclopentanone hemisolvate of lenalidomide was discovered in a nonmimetic gel.
• Selective crystallization of metastable lenalidomide Form 4 was achieved in an ethanol gel.
• Drug-mimetic gelator experiments showed no deviation from solution-phase polymorphic outcomes.

Conclusions:

• Non-mimetic gelators, particularly their fiber arrangement and confinement effects, significantly direct crystallization behavior.
• Spatial arrangement and confinement effects are critical factors in gel-phase crystallization control.
• Supramolecular gel crystallization offers a pathway to novel crystal forms and selective polymorph isolation.