Spectroscopic Monitoring of Carbamazepine Crystallization and Phase Transformation in Ethanol−Water Solution

Abstract

The crystallization mechanism of anhydrate/hydrate has to be understood in order to control the hydration state of an active pharmaceutical ingredient. In the present work, the formation of the anhydrous (CBZA) and dihydrate (CBZH) form of carbamazepine (CBZ) in ethanol−water solutions was studied by simultaneous monitoring of both the anhydrate/hydrate phase of the crystals and the CBZ concentration in the mother liquor with the Raman immersion probe. Two different cooling strategies and the effect of one surfactant were studied. The information obtained from the Raman spectroscopy indicated that the thermodynamic factor was dominated in determining the anhydrate/hydrate form of the crystals in the studied system. The thermodynamically stable form was obtained in all studied crystallization conditions. The presence of a surfactant additive showed a slight promotion effect only on the phase transformation of CBZA to CBZH. The results obtained in the present work lead to improved understanding of the formation mechanism of anhydrate/hydrate in aqueous solution.

Raman and ATR FTIR spectroscopy in reactive crystallization: Simultaneous monitoring of solute concentration and polymorphic state of the crystals

“…The PLS method has been reported in the literature as an appropriate method for the calibration of IR spectra, which are usually complex and rich in information but often non-specific [24,34]. The calibration procedure of this work has been described in a previous work [35].…”

“…The polymorphic or pseudopolymorphic composition of the crystals as a function of time can be obtained from the in-line Raman spectra, which provide valuable kinetic information on the phase transformation between different solid forms [18][19][20][21][22][23]. The application of Raman spectroscopy to a real complex multipolymorphic crystallization system was demonstrated in the literature [24]. The obtained inline phase composition profiles allowed improved process understanding, which led to more efficient optimization of the operation parameters to attain the desired solid form.…”

Quantitative In-Line Monitoring of Solvent-Mediated Polymorphic Transformation of Sulfamerazine by Near-Infrared Spectroscopy

“…14 Raman spectroscopy was applied to monitor the hydrate and anhydrate forms of cabamazepine during a cooling crystallization. 15 The thermodynamic factor matching well with Raman data was dominant in affecting the preferred crystal form. The reactive crystallization of the two polymorphs of L-glutamic acid was monitored using in-line Raman and attenuated total reflectance-Fourier transform infrared (ATR-FTIR) spectroscopy.…”

Raman Spectroscopy

“…Examples of solvent -mediated transformation monitoring include the conversion of anhydrous citric acid to the monohydrate form in water [235,236] , CBZ with water [237] and ethanol -water mixtures [238,239] , and cocrystallization studies of CBZ, caffeine, and theophylline with water [240] . Raman spectroscopy was used to monitor the crystallization rate and solute and solvent concentrations as griseofulvin was removed from an acetone solution using supercritical CO 2 as an antisolvent [241] .…”

“…CBZ has been used in several studies [238,239,243,244] . CBZ has been used in several studies [238,239,243,244] .…”