Online Classification of Mixed Co-Crystal and Solute Suspensions using Raman Spectroscopy

Abstract

This work seeks to develop a calibration-free statistical approach based on Raman spectroscopy for on-line identification of impurities during co-crystallization. Caffeine-glutaric acidacetonitrile was employed as the model system, which forms co-crystals from solution at appropriate conditions. Raman spectra were collected in three classes of suspensions with a solid mixture of caffeine crystals and co-crystals, pure co-crystals, and a mixture of glutaric acid crystals and co-crystals, respectively at different temperatures. These suspensions were used to represent the possible products of co-crystallization processes during which single component could crystallize out concomitantly with the desired co-crystal. A statistical model combining principal component analysis (PCA) and discriminant analysis (DA) was developed to classify these suspensions. PCA was first performed for these spectra and the resulting first few principal components were subjected to DA. It was found that the three classes of suspensions can be distinguished clearly by DA.

Semi‐heterogeneous Dual Nickel/Photocatalysis using Carbon Nitrides: Esterification of Carboxylic Acids with Aryl Halides

“…Para-substituted aryl iodides (1, 5, 6)react significantly faster than their meta analogues (13)(14)(15). With respect to the carboxylic acid coupling partner,awide array of substrates can be efficiently coupled, including aliphatic (16,19,21,22), olefinic (17), and benzylic (20, 24)carboxylic acids,aswell as benzoic acid derivatives (18,23). Carbonyl groups in the 2-position (31, 33)d on ot give the corresponding ester product.…”

Pharmaceutical solvates, hydrates and amorphous forms: A special emphasis on cocrystals

“…It becomes more important if some particular bands (mostly functional groups) are relatively sensitive to a particular solid form. Attenuated total reflectance (ATR) IR spectroscopy can be an important technique to study surface cocrystallization however ATR-IR has its own limitation in the characterization of polymorphs as it only penetrates the surface (no bulk penetration) [181,182]. Diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS) can also be a very useful technique to determine the nature and level of the interaction of solvent with the crystal or cocrystal in a hydrate or solvate, as it is a non-invasive technique and the hydrate/solvate can remain intact during analysis [183,184].…”

“…Raman spectroscopy is a very fast process analytical technology (PAT) tool which can be used to identify solid forms in drug substance and drug products [182]. Easy sample preparation is also another advantage of Raman spectroscopy, where unprocessed sample placed in a stainless steel or glass holder just needs to be interfaced with the laser beam [185].…”

Semi‐heterogene duale Nickel‐/Photokatalyse mit Kohlenstoffnitriden: Veresterung von Carbonsäuren mit Arylhalogeniden

“…[15] Um die Skalierbarkeit des photokatalytischen Systems zu untersuchen und bestimmen zu kçnnen, ob das photokatalytische System Licht unterschiedlicher Lichtquellen nutzen kann, wurde eine Methode zur Echtzeitmessung entwickelt. Durch In-situ-FTIR-Analyse wurde jegliche Stçrung durch den heterogenen Photokatalysator ausgeschlossen [23] und eine hochauflçsende Reaktionsverfolgung unter normalen Reaktionsbedingungen gewährleistet. [22] In diesem Reaktionssystem ist der Einsatz dieser Methode durch heterogene Komponenten, die zur Peak-Verbreiterung führen würden, und paramagnetischer Nickelverbindungen nicht vielversprechend.…”

“…[22] In diesem Reaktionssystem ist der Einsatz dieser Methode durch heterogene Komponenten, die zur Peak-Verbreiterung führen würden, und paramagnetischer Nickelverbindungen nicht vielversprechend. Durch In-situ-FTIR-Analyse wurde jegliche Stçrung durch den heterogenen Photokatalysator ausgeschlossen [23] und eine hochauflçsende Reaktionsverfolgung unter normalen Reaktionsbedingungen gewährleistet. Bei Beobachtung der Reaktion unter optimierten Reaktionsbedingungen wurde ein wachsender Peak bei ca.…”