Pushing Technique Boundaries to Probe Conformational Polymorphism

Area of Science:

• Solid-state chemistry
• Crystallography
• Materials science

Background:

• Understanding solid-state forms is crucial for drug development and manufacturing.
• Chlorpropamide (CPA) exhibits complex polymorphism that requires thorough investigation.

Purpose of the Study:

• To extensively explore the solid-form landscape of chlorpropamide (CPA).
• To discover and characterize new polymorphs and multicomponent forms of CPA.
• To demonstrate a combined experimental-computational approach for controlling polymorphism.

Main Methods:

• Flexible-molecule crystal structure prediction.
• Spray-drying experiments.
• Ball-milling.
• Impurity- and gel-assisted crystallization.

Main Results:

• New conformational polymorphs of CPA were obtained and contextualized.
• A novel metastable polymorph (ζ-CPA) was formed via spray-drying.
• The ball-milled η-form of CPA was identified and resolved.
• Novel multicomponent forms were successfully synthesized.

Conclusions:

• The combined experimental-computational approach effectively reveals and controls the formation of new metastable solid forms.
• This strategy enhances the understanding and manipulation of chlorpropamide polymorphism.
• The study highlights the potential for discovering novel solid forms with tailored properties.