Polymorphic Control in Pharmaceutical Gel-Mediated Crystallization: Exploiting Solvent-Gelator Synergy in FmocFF...

Area of Science:

• Materials Science
• Crystallization Science
• Pharmaceutical Science

Background:

• FmocFF is a versatile gelator enabling crystal engineering.
• Nilutamide exhibits complex polymorphism, posing challenges for drug formulation.
• Controlling crystallization pathways is crucial for pharmaceutical solid-state properties.

Purpose of the Study:

• To explore the synergistic effects of FmocFF organogels and solvent selection on nilutamide polymorphism.
• To achieve controlled crystallization and discover new nilutamide solid forms.
• To establish gel-mediated crystallization as a platform for pharmaceutical solid form discovery.

Main Methods:

• Systematic variation of solvent type and concentration in FmocFF organogels.
• Utilizing techniques such as Powder X-ray Diffraction (PXRD), Differential Scanning Calorimetry (DSC), Fourier-Transform Infrared Spectroscopy (FTIR), Single-Crystal X-ray Diffraction (SXRD), and Second-Harmonic Generation (SHG) microscopy.
• Investigating crystal nucleation and growth pathways under varying conditions.

Main Results:

• Remarkable control over nilutamide polymorphic outcomes was achieved.
• The first ambient-temperature isolation of pure nilutamide Form II was reported using an acetonitrile-based FmocFF organogel.
• A novel nilutamide polymorph with second-harmonic generation (SHG) activity was discovered, indicating potential non-centrosymmetric properties.
• A previously unreported nilutamide-chloroform solvate was characterized.

Conclusions:

• Solvent-specific molecular recognition within gel matrices allows access to new polymorphic spaces.
• Gel-mediated crystallization is a powerful and broadly applicable platform for discovering pharmaceutical solid forms under mild conditions.
• The findings highlight the potential of organogels in controlling drug polymorphism and discovering novel solid-state forms.