In-Line Monitoring of Carvedilol Crystallization Using Raman Spectroscopy

Abstract

Real-time Raman spectroscopy was used to characterize the solvent-mediated polymorphic transition and cooling crystallization of carvedilol. Kinetically preferred Form II was transformed into thermodynamically stable Form I during solvent-mediated phase transitions in ethyl acetate. The transition rate into Form I increased with rising temperature; however, at 0 °C a solvate form (Form VII) appeared. In the case of cooling crystallizations, the Form II polymorph was formed at 16−9 wt % drug concentration, while metastable solvates crystallized from a diluted, 2.9 wt % solution. A new solvate form, Form V*, was identified during crystallization in ethyl acetate, which is presumably related to Form V (known as an ethyl methyl ketone solvate in the literature). This study demonstrates the advantages of in-line Raman spectroscopy for monitoring in situ pharmaceutical crystallization by detecting the intermediate polymorphic transitions, which is fundamental in the development and operation of industrial crystallization processes.

Preparation and comparison of spray dried and electrospun bioresorbable drug delivery systems

“…The instrument is described elsewhere [21]. All spectra were detected over the range of 500-1800 cm À1 approximately 4 cm À1 resolution provided by a grating monochromator of 950 groove/mm.…”

Raman, UV, NIR, and Mid‐IR Spectroscopy with Focused Beam Reflectance Measurement in Monitoring Polymorphic Transformations

“…Mid-IR Discrimination between polymorphic forms of solids [11,12] ATR-UV/Vis Solvent-mediated polymorphic transformation monitoring in batch crystallization (changes in solute concentration) [13][14][15][16] NIR Determination of the polymorphic ratio of solid mixtures [17][18][19] NIR Solvent-mediated polymorphic transformation monitoring [18,20] Raman Determination of the polymorphic ratio of solid mixtures [21][22][23][24][25] FT-Raman, FTIR Comparison between the two techniques in determining the polymorphic ratio of solid mixtures [26,27] Raman Cocrystallization of carbamazepine and nicotinamide monitoring [28] Raman Solvent-mediated polymorphic transformation monitoring [29,30] Raman, FBRM, PVM Study on the impact of operating parameters on polymorphic transformation of D-mannitol [31] Raman Measurement of the total solid concentration in a polymorphic system [32,33] Raman Measurement of solute concentration in a polymorphic system [34,35] FBRM Solvent-mediated polymorphic transformation monitoring [36][37][38][39][40] Raman, NIR, UV/Vis Solvent-mediated polymorphic transformation monitoring [41,42] Raman Feedback strategies to control polymorphs of carvedilol [43,44] Raman, NIR Application of quantitative Raman spectroscopy using a good calibration practice (GCP) procedure [45] a) b) Crystallization Process Informatics System (Cry-PRINS) software. CryPRINS provides a communication interface via file transfer, OPC (Object linking and embedding ...…”

Inline Monitoring of Taltirelin Crystallization in Batch Cooling Mode Using Raman Spectroscopy

“…It is particularly effective since it provides fast, nondestructive examination and is remarkably suitable for distinguishing polymorphs due to the sharp and selective vibrational bands 1. Recently, Raman spectroscopy has been used to inline monitor quantitatively in pharmaceutical field 2–6. This technique proved to be a suitable tool for in‐line monitoring of polymorphic crystallization because the Raman spectra offer information about both the solution phase and the solid phase 4, 7–10.…”