Spatially offset raman spectroscopy for monitoring solvent content during pharmaceutical drying Mais Al-Attili 1 , Carla Ferreira 1 , Chris Price 2 , Karen Faulds 3 and Yi-Chieh Chen 1 1 Department of Chemical and Process Engineering, University of Strathclyde, Glasgow, UK, 2 ESPRC Centre for Innovative Manufacturing in Continuous Manufacturing and Crystallisation, University of Strathclyde, Glasgow, UK, 3 Department of Pure and Applied Chemistry, University of Strathclyde, Glasgow, UK Drying is a complex process that affects critical quality attributes of the final pharmaceutical product. Non- uniformity of drying is a particular issue impeding the optimisation of this process [1]. Conventional Raman measurements collect backscattered Raman signals and are suitable for monitoring uniform systems, but fall short with monitoring non-uniform systems due to the limited depth from which signals are collected. Spatially offset Raman spectroscopy (SORS) collects spectra from positions offset from the incident light, providing information about depths beyond those offered by conventional Raman measurements [2]. This study uses a bespoke SORS probe to monitor agitated drying of two grades of paracetamol, granular and powder, in anisole. The probe illuminates laser at 45˚ and collects backscattering signals and signals from 1-5 mm equidistant offsets. Several runs were conducted for both grades and loss on drying measurements were used for reference. Spectra from different configurations were analysed using partial least square regression (PLSR) analysis. The merit of the models was described using root mean square error of cross-validation (RMSECV) and prediction (RMSEP), R 2 , prediction and residuals plots, and loadings and scores of the models. Multiple wavenumber ranges and pre-processing methods were evaluated for improving the model performance. 4-mm and 0-mm offsets were found to be optimal for granular and powder grades, respectively, with an RMSECV and RMSEP of 0.6% for granular paracetamol and RMSECV of 1.1% and RMSEP of 1.3% for powder paracetamol. The result from different grades suggest a potential for SORS to monitor particle size, in addition to solvent content. References 1. Conder EW, Cosbie AS, Gaertner J, Hicks W, Huggins S, MacLeod CS, Remy B, Yang BS, Engstrom JD, Lamberto DJ, Papageorgiou CD Organic Process Research and Development 2017, 21, 420. 2. Matousek P, Clark IP, Draper ERC, Morris MD, Goodship AE, Everall N, Towrie M, Finney WF, Parker AW Applied Spectroscopy 2005, 59, 393.
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