In Situ Monitoring of Crystalline Transformation of Carbamazepine Using Probe-Type Low-Frequency Raman Spectroscopy

Abstract

Crystallization is one of the most useful processes for the separation and purification of crystalline compounds. In crystallization processes, real-time monitoring is essential to obtain constant quality of crystalline compounds. This paper is the first to report in situ monitoring of crystalline transformations of active pharmaceutical ingredients by probe-type low-frequency Raman spectroscopy. In this study, carbamazepine was used as a model active pharmaceutical ingredient. We attempted to monitor the crystalline transformation of carbamazepine during heat treatment and the addition of solvent in a one-pot reaction. When carbamazepine form III was heated to 170 °C, the indicative spectrum of carbamazepine form I appeared over time. Subsequent addition of ethanol with heat treatment caused the carbamazepine form I spectrum to disappear. After cooling to room temperature, the spectrum of carbamazepine form III reappeared. To optimize the solvent ratio, we monitored carbamazepine form III as it dispersed into a mixture of ethanol/water with different compositions (75/ 25, 62.5/37.5, 50/50, 37.5/62.5, and 25/75 (v/v)). The spectra of carbamazepine dihydrate were observed in all solvent compositions. When the mixture of ethanol/water was 62.5/37.5 (v/v), the conversion time to carbamazepine dihydrate was fastest. Therefore, probe-type lowfrequency Raman spectroscopy can be used for the in situ monitoring of crystalline transformation and may become a useful process analytical technology technique.

Unravelling Defect Passivation Mechanisms in Sulfur-treated Sb2Se3

“…Long-range order induces AVM enhancement thus revealing otherwise hidden LFRS modes. [21,22] AVMs of Sb2Se3 have been extensively studied using DFT-based theoretical models. Figure 4b represents the LFRS spectrum of the Sb2Se3 samples before and after sulfur treatment.…”

Contribution of low-frequency Raman spectroscopy to determine the solubility curves of drugs in polymers: The case of paracetamol/PVP

“…The present study shows the capabilities of LFRS for identifying and quantitatively determining crystalline polymorph, directly and rapidly within solid dispersions. It is now recognized that LFRS can be used for the polymorph characterization of APIs 27,28 . We have previously developed a direct method based on LFRS measurements providing very fast and accurate quantification of crystalline fraction along isothermal and non-isothermal devitrification processes 22,29 .…”

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.…”