Raman spectroscopy for quantitative analysis of pharmaceutical solids

Abstract

Raman spectroscopy is experiencing a surge in interest in solid-state pharmaceutical applications. It is rapid, non-destructive, no sample preparation is required and measurements can be made in aqueous environments. It can be used for not only qualitative, but also quantitative, analysis. In this paper, the use of Raman spectroscopy for quantitative analysis of pharmaceutical solids is reviewed. The technique has been used for chemical and physical form analysis. Physical form analysis has involved quantification of polymorphism, hydrates, the amorphous form and, recently, protein conformation. Initially, simple powder systems were quantified, although this has since extended to complex pharmaceutical formulations, including tablets, capsules, microspheres and suspensions. Formulations have also been analysed through packaging. The characteristics of the technique make it ideal for process monitoring and it has been used to quantify changes in-situ during processes such as wet granulation and batch crystallisation. The theoretical basis of quantitative Raman spectroscopy, common data analysis approaches, including multivariate analysis, and sources of error in quantitative analysis are also discussed.

Fast real-time monitoring of entacapone crystallization and characterization of polymorphs via Raman spectroscopy, statistics and SWAXS

“…Thus, the analysis of in-line Raman spectra obtained during the crystallization process could reveal polymorphic transformations as a function of time. Quantitative crystallization monitoring by in-line Raman spectroscopy usually involves the design of calibration models derived from the Raman spectra of pure solid-state forms (13)(14)(15)(16)(17).…”

Molecular characterization of drug´s nanocarriers based on plasmon-enhanced spectroscopy: Fluorescence (SEF) and Raman (SERS)

“…Como la IM es insoluble en agua a las concentraciones necesarias para obtener espectro Raman, se presenta el espectro en disolución en DMSO. El perfil espectral en disolución, muy semejante al de la IM sólida, permite afirmar que existen dímeros en disolución como ocurre en el sólido [7,28,33]. Utilizando además los datos del espectro Raman Resonante de la IM en disolución excitando a 325 nm (no mostrados aquí), es posible asignar algunas bandas a los grupos indol (I) y benzoilo (B) así como a los sustituyentes del último (C-Cl, C=O).…”

Quantitative polymorph contaminant analysis in tablets using Raman and near infra-red spectroscopies

“…[10][11][12][13] Many APIs are ideal for study by Raman as 5 they are typically strong Raman scatters due to the presence of aromatic functional groups with 6 symmetric vibrational modes. [10] Raman, like NIR, allows for minimal if any sample preparation 7…”

“…However, 7 many newer Raman systems have much improved Rayleigh rejection filtering which provide 8 access to this region and it will become much more common for the routine analysis of 9 pharmaceutical solids suing Benchtop instrumentation. 10 It is easy to distinguish the differences between polymorphs from the spectra of the pure 11 materials, and for simple binary mixtures it is also comparatively easy to observe the presence of 12 both polymorphs by visual inspection and simple chemometrics.…”

“…Eliminating the noise issue for the TRS data can easily be achieved by the 9 averaging of multiple spectra, although this would reduce the high throughput somewhat. 10 Apart from the purely signal based considerations, TRS is also better from a sampling 11 perspective in that with an 8 mm diameter spot size compared to the 200 m the surface area 12 sampled is ~100 times greater. Overall the TRS samples ~38% of the tablet surface whereas the 13 BR only manages a paltry 0.4%, (Calculated by calculating surface area of 200 m spot size and 14 multiplying by 16 as a 4x4 grid was used here), and the consequences of this are also evident in the 15 quantitative analysis discussed below.…”