Advanced Calibration Strategy for in Situ Quantitative Monitoring of Phase Transition Processes in Suspensions Using FT-Raman Spectroscopy

Abstract

There is an increasing interest in using Raman spectroscopy to identify polymorphic forms and monitor phase changes in pharmaceutical products for quality control. Compared with other analytical techniques for the identification of polymorphs such as X-ray powder diffractometry and infrared spectroscopy, FT-Raman spectroscopy has the advantages of enabling fast, in situ, and nondestructive measurements of complex systems such as suspension samples. However, for suspension samples, Raman intensities depend on the analyte concentrations as well as the particle size, overall solid content, and homogeneity of the solid phase in the mixtures, which makes quantitative Raman analysis rather difficult. In this contribution, an advanced model has been derived to explicitly account for the confounding effects of a sample's physical properties on Raman intensities. On the basis of this model, a unique calibration strategy called multiplicative effects correction (MEC) was proposed to separate the Raman contributions due to changes in analyte concentration from those caused by the multiplicative confounding effects of the sample's physical properties. MEC has been applied to predict the anhydrate concentrations from in situ FT-Raman measurements made during the crystallization and phase transition processes of citric acid in water. The experimental results show that MEC can effectively correct for the confounding effects of the particle size and overall solid content of the solid phase on Raman intensities and, therefore, provide much more accurate in situ quantitative predictions of anhydrate concentration during crystallization and phase transition processes than traditional PLS calibration methods.

Insitu Raman spectroscopic observation of sequential hydrolysis of stannous chloride to abhurite, hydroromarchite, and romarchite

“…appeared to track the consumption and generation of each species effectively, they should be interpreted with caution since many factors could influence the Raman signal intensity. Many previous publications have demonstrated that particle size in a suspension could influence Raman signals via different mechanisms . For example, small particle size leads to larger surface area, thereby increasing the amount of material that can be effectively excited and leading to a stronger Raman signal.…”

A stainless steel multi‐well plate (SS‐MWP) for high‐throughput Raman analysis of dilute solutions

“…[1][2][3][4][5][6] The minimal sample preparation required also makes this technique suitable for high-throughput analysis. Furthermore, the detail in Raman spectra provides information on the molecular properties and composition of the sample which can be used for identification and quality control purposes.…”

Quantitative analysis based on spectral shape deformation: A review of the theory and its applications

“…Since SSD extracts quantitative information of the analyte of interest from SSD rather than variations in absolute spectral intensities, it has the potential to realize accurate quantification of particulate systems using Raman spectroscopy. SSD was applied to the monitoring of the anhydrate concentrations from in situ Fourier Transform (FT)‐Raman measurements made during the crystallization and phase transition processes of citric acid in water . It effectively mitigated the confounding effects of the overall solid content of the solid phase on Raman intensities and hence provided much more accurate in situ quantitative predictions of anhydrate concentration during crystallization and phase transition processes than traditional PLS calibration methods.…”