Drug–excipient interactions in ketoprofen: A vibrational spectroscopy study

Abstract

Ketoprofen (3-benzoyl-alpha-methylbenzeneacetic acid) is a widely used nonsteroidal anti-inflammatory drug (NSAID), always administered in the form of drug-excipient physical mixtures (PMs). The occurrence of possible interactions between ketoprofen and two commonly used excipients-lactose (LAC) and polyvinylpyrrolidone (PVP)-was evaluated, through vibrational spectroscopy techniques [both Raman and Inelastic Neutron Scattering (INS)]. Spectral evidence of drug:excipient close contacts, which were enhanced by aging, was verified for the (1:1) (w:w) (ketoprofen:PVP) and (ketoprofen:LAC) PMs, both by Raman and INS. These interactions were found to involve mainly the central carbonyl and the terminal methyl-carboxylic moieties of the ketoprofen molecule, this being reflected in particular vibrational modes, such as the methyl torsion, the out-of-plane C-OH bending, and the inter-ring C=O stretching.