TY - JOUR

T1 - Exploring the Solid-State Landscape of Carbamazepine during Dehydration

T2 - A Low Frequency Raman Spectroscopy Perspective

AU - Remoto, Peter I.I.I.J.G.

AU - Bērziņš, Kārlis

AU - Fraser-Miller, Sara J.

AU - Korter, Timothy M.

AU - Rades, Thomas

AU - Rantanen, Jukka

AU - Gordon, Keith C.

N1 - Funding Information: S. Miller is supported by a Royal Society Te Apārangi, Marsden fast-start (grant number 19-UOO-210) and a MBIE smart idea (grant number UOOX1907). S. Miller and K. Gordon are funded by Te Whai Ao, the Dodd-Walls Centre for photonic and quantum technologies (a NZ Centre of Research Excellence). Funding Information: The authors gratefully acknowledge New Zealand eScience Infrastructure (NeSI) for the high-performance computing facilities and support from the Dodd-Walls Centre for Photonic and Quantum Technologies. Publisher Copyright: © 2023 by the authors.

PY - 2023

Y1 - 2023

N2 - The solid-state landscape of carbamazepine during its dehydration was explored using Raman spectroscopy in the low- (−300 to −15, 15 to 300) and mid- (300 to 1800 cm−1) frequency spectral regions. Carbamazepine dihydrate and forms I, III, and IV were also characterized using density functional theory with periodic boundary conditions and showed good agreement with experimental Raman spectra with mean average deviations less than 10 cm−1. The dehydration of carbamazepine dihydrate was examined under different temperatures (40, 45, 50, 55, and 60 °C). Principal component analysis and multivariate curve resolution were used to explore the transformation pathways of different solid-state forms during the dehydration of carbamazepine dihydrate. The low-frequency Raman domain was able to detect the rapid growth and subsequent decline of carbamazepine form IV, which was not as effectively observed by mid-frequency Raman spectroscopy. These results showcased the potential benefits of low-frequency Raman spectroscopy for pharmaceutical process monitoring and control.

AB - The solid-state landscape of carbamazepine during its dehydration was explored using Raman spectroscopy in the low- (−300 to −15, 15 to 300) and mid- (300 to 1800 cm−1) frequency spectral regions. Carbamazepine dihydrate and forms I, III, and IV were also characterized using density functional theory with periodic boundary conditions and showed good agreement with experimental Raman spectra with mean average deviations less than 10 cm−1. The dehydration of carbamazepine dihydrate was examined under different temperatures (40, 45, 50, 55, and 60 °C). Principal component analysis and multivariate curve resolution were used to explore the transformation pathways of different solid-state forms during the dehydration of carbamazepine dihydrate. The low-frequency Raman domain was able to detect the rapid growth and subsequent decline of carbamazepine form IV, which was not as effectively observed by mid-frequency Raman spectroscopy. These results showcased the potential benefits of low-frequency Raman spectroscopy for pharmaceutical process monitoring and control.

KW - carbamazepine

KW - dehydration

KW - low-frequency Raman spectroscopy

KW - polymorphism

KW - solid-state

KW - THz Raman spectroscopy

U2 - 10.3390/pharmaceutics15051526

DO - 10.3390/pharmaceutics15051526

M3 - Journal article

C2 - 37242768

AN - SCOPUS:85160400768

VL - 15

JO - Pharmaceutics

JF - Pharmaceutics

SN - 1999-4923

IS - 5

M1 - 1526

ER -