Conformational Landscape, Polymorphism, and Solid Forms Design of Bicalutamide: A Review.

Area of Science:

• Pharmaceutical Sciences
• Solid-State Chemistry
• Drug Delivery

Background:

• Bicalutamide (BCL), a non-steroidal antiandrogen, displays significant conformational polymorphism.
• Its solid-state behavior critically impacts physicochemical and biopharmaceutical properties.

Purpose of the Study:

• To review and integrate computational and experimental findings on BCL's structural features and polymorphism.
• To examine factors influencing polymorph stability, solubility, and dissolution kinetics.
• To explore advanced solid-state optimization strategies and supercritical fluid technologies for BCL.

Main Methods:

• Comprehensive literature review of computational and experimental studies.
• Analysis of torsional flexibility, hydrogen bonding, π-π stacking, and F-F contacts.
• Synthesis of data on co-crystals, solvates, amorphous forms, solid dispersions, and SCF technologies.

Main Results:

• Identified key factors (torsional flexibility, H-bonds, π-π stacking, F-F contacts) affecting BCL polymorph stability and dissolution.
• Summarized advances in solid-state engineering for BCL, including co-crystals and amorphous forms.
• Highlighted the potential of supercritical fluid technologies for particle engineering and dissolution enhancement.

Conclusions:

• A framework is provided for designing next-generation BCL solid forms.
• Enhanced bioavailability and stability can be achieved by linking molecular insights with formulation strategies.
• Further research into solid-state optimization holds promise for improving BCL's therapeutic efficacy.