title: 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.
authors.affiliation: Centre for Process Analytics and Control Technology, Department of Pure and Applied Chemistry, University of Strathclyde, Glasgow, G1 1XL, Scotland, UK. z.p.chen@ncl.ac.uk
authors.forename: Zeng-Ping
authors.initials: ZP
authors.lastname: Chen
authors.forename: Gilles
authors.initials: G
authors.lastname: Fevotte
authors.forename: Alexandre
authors.initials: A
authors.lastname: Caillet
authors.forename: David
authors.initials: D
authors.lastname: Littlejohn
authors.forename: Julian
authors.initials: J
authors.lastname: Morris
mesh_terms: D002138:Calibration; D005583:Fourier Analysis; D010316:Particle Size; D044367:Phase Transition; D012680:Sensitivity and Specificity; D012997:Solvents / Q000737:chemistry; D013059:Spectrum Analysis, Raman / Q000379:methods*; D013535:Suspensions; D013997:Time Factors
chemical_list: D012997:Solvents; D013535:Suspensions