Solid-state cocrystal formation between acyclovir and fumaric acid: Terahertz and Raman vibrational spectroscopic...

Area of Science:

• Solid-state chemistry
• Materials science
• Spectroscopy

Background:

• Acyclovir and fumaric acid are important pharmaceutical compounds.
• Cocrystal formation can alter the physicochemical properties of active pharmaceutical ingredients.
• Understanding cocrystal structures is crucial for drug development.

Purpose of the Study:

• To investigate the vibrational properties of solid-state acyclovir-fumaric acid cocrystals.
• To compare the spectral characteristics of the cocrystal with its individual components.
• To elucidate the structural basis of cocrystal formation using computational methods.

Main Methods:

• Terahertz time-domain spectroscopy (THz-TDS) at room temperature.
• Raman spectroscopy at room temperature.
• Density functional theory (DFT) calculations for vibrational mode simulation.

Main Results:

• Experimental THz spectra showed distinct absorption peaks for the cocrystal (0.65, 0.94, 1.10 THz) absent in raw materials.
• Raman spectra also revealed significant differences between the cocrystal and its constituents.
• DFT simulations identified a dimer cocrystal form stabilized by hydrogen bonding between acyclovir and fumaric acid, with calculated THz peaks (0.70, 1.01, 1.34 THz) aligning with experimental data.
• Theoretical Raman spectra supported the experimental findings for the dimer form.

Conclusions:

• The study successfully characterized the vibrational spectra of acyclovir-fumaric acid cocrystals.
• Hydrogen bonding between specific functional groups (O8C7N1H27 and COOH) is key to forming the observed dimer cocrystal structure.
• DFT calculations provide valuable insights into cocrystal formation and aid in assigning characteristic spectral bands.