Recent progress of structural study of polymorphic pharmaceutical drugs

Area of Science:

• Solid-state chemistry
• Pharmaceutical sciences
• Crystallography

Background:

• Active pharmaceutical ingredient (API) polymorphism is critical for drug efficacy and manufacturing.
• Despite extensive study, new polymorphic forms of established drugs continue to be discovered.
• Understanding and controlling polymorphism is an ongoing challenge in pharmaceutical development.

Purpose of the Study:

• To review advances in understanding API polymorphism since 2010, focusing on structural aspects.
• To highlight the discovery of new polymorphs for extensively studied drugs.
• To discuss structure-based methods and analytical techniques driving polymorphism research.

Main Methods:

• Review of literature on API polymorphism, emphasizing structural viewpoints.
• Analysis of advances in preparative techniques beyond conventional solvent, temperature, and pressure modifications.
• Examination of the role of advanced analytical techniques (X-ray, spectroscopy, microscopy) and computational simulations.

Main Results:

• New polymorphs have been identified for most of the twelve model drugs reviewed, even those previously considered well-characterized.
• Structure-based approaches have proven successful in yielding novel polymorphic forms.
• Advanced analytical and computational tools have significantly aided in identifying, characterizing, and predicting the stability of polymorphs.

Conclusions:

• Recent advancements in structure-based methods, analytical techniques, and computational simulations have enhanced the discovery of new API polymorphs.
• These insights are crucial for controlling polymorphic forms throughout drug manufacturing and formulation.
• Continued research in this area promises improved drug development and product quality.