Polymorphism and crystallization of active pharmaceutical ingredients (APIs)

Area of Science:

• Pharmaceutical Sciences
• Solid-State Chemistry
• Materials Science

Background:

• Active pharmaceutical ingredients (APIs) exist in various solid forms, including polymorphs, salts, and amorphous solids.
• These diverse solid forms possess distinct properties influencing drug bioavailability, stability, and performance.
• Selecting the appropriate API solid form is critical for successful drug product development.

Purpose of the Study:

• To provide a comprehensive overview of the thermodynamics and kinetics of polymorphic systems.
• To discuss the characterization techniques for various API solid forms.
• To review recent advancements in API solid-form discovery and control.

Main Methods:

• Thermodynamic and kinetic analysis of polymorphic systems.
• Solid-state characterization techniques (e.g., diffraction, spectroscopy, thermal analysis).
• Review of established and emerging methods for polymorph screening and selection.

Main Results:

• Different solid forms of APIs exhibit significantly varied physicochemical and performance characteristics.
• Understanding solid-form behavior is essential for predicting and controlling drug product attributes.
• Numerous techniques have been developed for the effective discovery, characterization, and control of API solid forms.

Conclusions:

• The selection of the optimal API solid form is a critical step in pharmaceutical development.
• A deep understanding of solid-state properties and transformation pathways is necessary.
• Advanced techniques facilitate the discovery and control of desired API solid forms for improved drug products.