Correlation between the conformational crossover of carbamazepine and its polymorphic transition in supercritical CO2: On the way to polymorph control

•Analysis of the conformations of carbamazepine molecules in scCO2 was performed.•Conformational crossover was found under isochoric heating conditions.•Polymorphic transition was found in solid carbamazepine being in contact with scCO2.•Correlation between conformations and polymorphism of carbamaz...

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Bibliographic Details
Published in:European journal of pharmaceutical sciences 2020-04, Vol.146, p.105273-105273, Article 105273
Main Authors: Oparin, Roman D., Kurskaya, Maria V., Krestyaninov, Michael A., Idrissi, Abdenacer, Kiselev, Michael G.
Format: Article
Language:English
Subjects:
Carbamazepine
Chemical Sciences
Conformational Equilibria
IR spectroscopy
or physical chemistry
Polymorphism
Quantum Chemical Calculations
Raman spectroscopy
Supercritical CO2
Theoretical and
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Summary:•Analysis of the conformations of carbamazepine molecules in scCO2 was performed.•Conformational crossover was found under isochoric heating conditions.•Polymorphic transition was found in solid carbamazepine being in contact with scCO2.•Correlation between conformations and polymorphism of carbamazepine was stated. In this paper we have established a correlation between the conformation crossover of carbamazepine and associated polymorph transformation. This was achieved by using a combination of quantum chemical calculations and in situ IR spectroscopy for performing a conformational analysis of carbamazepine molecules in its saturated solution in scCO2 being in permanent contact with the carbamazepine solid form. Using quantum calculations, we determined two carbamazepine conformers, whose spectral signatures were then found in experimental IR spectra. Further analysis of the IR spectra allowed us to quantify the distribution of these conformations in supercritical CO2. We found that this distribution can be changed by heating from 40°C to 110°C along two isochores at 1.1 and 1.3 of the critical CO2 density. Using in situ Raman spectroscopy we proved that the appearing conformational crossover correlates with the polymorphic transformation of the carbamazepine solid form. Moreover, this transformation was proved by the results of IR diffuse reflection spectroscopy. [Display omitted]
ISSN:0928-0987
1879-0720
DOI:10.1016/j.ejps.2020.105273