Combining Nuclear Magnetic Resonance Spectroscopy and Density Functional Theory Calculations to Characterize...

Area of Science:

• Solid-state chemistry
• Materials science
• Computational chemistry

Background:

• Carvedilol exists in multiple crystalline forms (polymorphs) and hydrates.
• Understanding these forms is crucial for drug formulation and efficacy.
• Solid-state Nuclear Magnetic Resonance (NMR) spectroscopy is a powerful tool for characterizing solid materials.

Purpose of the Study:

• To comprehensively understand the crystalline forms of carvedilol.
• To investigate carvedilol form II, form III, and its hydrate.
• To correlate experimental NMR data with theoretical calculations.

Main Methods:

• Solid-state NMR experiments using Carbon-13 (13C) and Nitrogen-15 (15N) cross-polarization magic-angle spinning (CP MAS).
• Density Functional Theory (DFT) calculations employing the Gauge-Including Projector-Augmented Wave (GIPAW) method.
• Simulation of 13C and 15N chemical shifts.

Main Results:

• Experimental 13C and 15N CP MAS NMR spectra were obtained for carvedilol form II, form III, and hydrate.
• DFT calculations accurately predicted the 13C and 15N chemical shifts for the studied carvedilol polymorphs.
• A very good agreement was observed between the experimental and calculated NMR chemical shifts.

Conclusions:

• The study provides a comprehensive understanding of carvedilol crystalline forms.
• The combination of solid-state NMR and DFT calculations is effective for characterizing drug polymorphs.
• The findings validate the use of GIPAW DFT for simulating NMR chemical shifts in carvedilol systems.