DFT and temperature-dependent Raman spectroscopic study of gabapentin polymorphism and determination of its dominant conformer in human serum

Abstract

The clinically important drug gabapentin (GBP) exhibits polymorphism, crystallizing in multiple forms (α, β and γ) that differ in molecular packing and spectroscopic signatures. The α, β and γ polymorphs of GBP have been extensively examined through temperature-dependent Raman spectroscopy and density functional theory (DFT) analysis. Temperature-dependent Raman spectra suggested the polymorphic phase transitions with temperature. The α form is predominant at room temperature. The α → β phase transition is observed at ∼150 °C and β → γ phase transition is observed at∼170 °C. These results imply that GBP possesses many different polymorphs, reflecting many conformational states accessible to the molecule. Surface-enhanced Raman spectroscopy (SERS) measurements of GBP in aqueous medium and human serum enable the direct identification of the β-conformer both upon hydration and within the complex biological matrix.