Identification and characterization of pharmaceuticals using Raman and surface‐enhanced Raman scattering

Abstract

Many recent papers reflect ongoing research and development concerning pharmaceutical applications of Raman techniques. This short review highlights different Raman techniques (dispersive, Fourier transform, resonance Raman, SERS, SERRS, FT-SERS) employed in pharmaceutical investigations. Several Raman applications such as fundamental structural investigations, quantitative analysis, drug-excipient interaction, formulation, limit of detection, pH-dependent pharmaceutical species, adsorption geometry at a given surface and functional groups involved in adsorption for several widely used pharmaceutical compounds are presented.

Surface-enhanced Raman Spectroscopy for Trace Identification of Controlled Substances: Morphine, Codeine, and Hydrocodone

“…The potential of SERS especially in forensic science, fields of trace evidence, the analysis of sub‐milligram size samples of controlled substances, and questioned documents has been recently highlighted in a review of analytical tools for forensic science (1). Research so far has shown that SERS can be effectively applied to problems, such as the discrimination of jet printer inks in situ (4), inks from ball point pens (5), the rapid identification of synthetic dyes on fiber samples (6), the sensitive determination of narcotics (7), and other controlled substances (8), such as amphetamines (9), cocaine, and nicotine (10). Normal Raman spectra of morphine hydrochloride (11) and codeine phosphate (12) have been previously reported, as well as the SERS spectrum of codeine using a silver surface formed photolytically by the probe laser as the SERS substrate (13).…”

SERS and Pharmaceuticals

“…The orientation of the 5-fluorouracil molecules on the AgNP surface was then determined with the help of SERS surface selection rules [1][2][3][4]. These state that vibrations deriving their intensities from a large value of α zz (the z axis parallel to the surface normal) would be the most intense in the SERS spectrum when the molecule has a perpendicular orientation to the metal surface [44,45].…”

“…The advantages of SERS include detection limits at the parts-per-billion level or lower, real-time response, qualitative and quantitative capabilities, a high degree of specificity, simultaneous multiplex detection and trace analysis (see also Chapters 3,4 and 5). SERS can also be used as a surface investigative tool [1]. It can provide valuable information about the changes in molecular identity of the drug substance and its orientation with respect to the SERS substrate under different physiological conditions (e.g.…”

“…It can provide valuable information about the changes in molecular identity of the drug substance and its orientation with respect to the SERS substrate under different physiological conditions (e.g. pH and concentration) [1]. It should be noted that the type and morphology of the SERS-active substrate (see also Chapter 2) are responsible for the chemical nature and geometry of the adsorbed drug species as well as for the enhancement of the SERS signal (see also Chapter 1).…”

Discriminating polymorph distributions in pharmaceutical tablets using stimulated Raman scattering microscopy

“…Unlike TGA or DSC, vibrational spectroscopy techniques such as infrared absorption and Raman scattering are interesting because they directly address the vibrational signature of molecular bonds present within a sample . For instance, Raman spectroscopy is widely used in the pharmaceutical industry because it is non‐destructive, only a simple preparation is required and it enables to investigate polymorphism in amorphous materials, which is not the case when using XRPD . However, spontaneous Raman spectroscopy suffers from a low cross section that results in long acquisition times and makes molecular mapping time consuming .…”