In Situ Monitoring of Antisolvent Cocrystallization by Combining Near-Infrared and Raman Spectroscopies

Abstract

In situ monitoring techniques are essential for the control and optimization of the cocrystallization process. In our previous study, we successfully monitored indomethacin−saccharin (IMC−SAC) cocrystallization by antisolvent addition using a method based on near-infrared principal component analysis (NIR−PCA). In this study, a calibration model was developed to predict the solute concentration of the two components. Several samples withdrawn from five sets of experiments were used to develop the calibration model. The actual concentrations of the two components were determined using UV−vis spectroscopy and high performance liquid chromatography (HPLC). The amount of solid-phase material in suspension was calculated from these solute concentration data. Correlations between NIR spectra and solid concentrations were evaluated using partial least-squares (PLS) regression analyses. Reasonably good calibration models with determination coefficients (R 2 ) higher than 0.979 were obtained. Process monitoring was performed using in situ NIR and Raman spectroscopies to predict the concentrations of both IMC and SAC in solution and to identify the solid-phase materials, respectively. The calibration models were deemed suitable, with reasonable accuracy and precision, for in situ concentration monitoring of the antisolvent crystallization of IMC− SAC cocrystals. This combination of NIR and Raman spectroscopies was able to detect the formation and phase transition of the resulting cocrystal.

Pharmaceutical Cocrystals: New Solid Phase Modification Approaches for the Formulation of APIs

“…The technique was considered to be sensitive due to the appearance of new peaks in the region 4800–5200 cm −1 , and it was eventually proposed for the control of the purity of cocrystals on an industrial scale. However, Raman shows better accuracy and sensitivity, and has been used for formation evaluation and in situ monitoring of cocrystallization either by itself or in combination with NIR [ 128 , 129 ].…”

Engineering Cocrystals of Poorly Water-Soluble Drugs to Enhance Dissolution in Aqueous Medium

“…In addition to the characterization techniques discussed above, some of the well-advanced techniques such as pair-distribution function PXRD [ 224 ], Terahertz (THz) spectroscopic imaging [ 225 ], Probe-Type Low-Frequency Raman Spectroscopy [ 226 ], combined near IR and Raman spectroscopies [ 227 ], in situ Raman spectroscopy, in situthermomicroscopy [ 192 ], calorimetric analysis [ 192 ] and PAT [ 75 ] are being used widely by many researchers nowadays in order to understand the phase transition events that possibly occur during a cocrystallization process.…”

Thermodynamic mechanism of selective cocrystallization explored by MD simulation and phase diagram analysis

“…With the help of Raman spectroscopy, Kyeong‐Sill Lee and his coworkers monitored the formation of salicylic acid‐4,4′‐dipyridyl cocrystals in solution . Min‐Jeong Lee et al detected the phase transition of indomethacin‐saccharin cocrystals …”