Abstract
Carbamazepine (CBZ), a widely used anticonvulsant drug, can crystallize and exhibits four polymorphic forms and one dihydrate. Anhydrous CBZ can spontaneously absorb water and convert to the hydrate form whose different crystallinity leads to lower biological activity. The present study was concerned to the possibility of recovering the hydrated form by heating. The thermal behavior of spontaneously hydrated carbamazepine was investigated by TG/DTG-DTA and DSC in dynamic atmospheres of air and nitrogen, which revealed that the spontaneous hydration of this pharmaceutical resulted in a Form III hydrate with 1.5 water molecules. After dehydration, this anhydrous Form III converted to Form I, which melted and decomposed in a single event, releasing isocyanic acid, as shown by evolved gas analysis using TG-FTIR. Differential scanning calorimetry analyses revealed that Form III melted and crystallized as Form I, and that subsequent cooling cycles only generated Form I by crystallization. Solid state decomposition kinetic studies showed that there was no change in the substance after the elimination of water by heating to 120 °C. Activation energies of 98 ± 2 and 93 ± 2 kJ mol-1 were found for the hydrated and dried samples, respectively, and similar profiles of activation energy as a function of conversion factor were observed for these samples.
Highlights
Carbamazepine (CBZ) (Figure 1), 5H-dibenz(b,f)azepine-5-carboxamide, is a white or almost white crystalline powder that is used as a first-generation anticonvulsant drug to treat epilepsy, trigeminal neuralgia, manic-depressive illness, and explosive aggression
The present investigation showed that Form III of anhydrous CBZ can become spontaneously hydrated, Prof
The TG results showed that the first step of mass loss was completed and that no further decomposition occurred
Summary
Carbamazepine (CBZ) (Figure 1), 5H-dibenz(b,f)azepine-5-carboxamide, is a white or almost white crystalline powder that is used as a first-generation anticonvulsant drug to treat epilepsy, trigeminal neuralgia, manic-depressive illness, and explosive aggression. At least four polymorphs and a dehydrate, as well as other solvates of CBZ, have been described in the literature (Qu, Louhi-Kultanen, Kallas, 2006; O’Mahony et al, 2012). The most stable known anhydrous form under room conditions is Form III. It is known that in a humid environment, the anhydrates take up water and convert to the hydrates (Liu, Dang, Wei, 2012). Forms I and III of the drug constitute an enantiotropic pair, whose relative thermodynamic stability changes at 70 °C. This temperature, Form III is most stable, while above this temperature, Form I becomes more stable (McGregor et al, 2004; Behme, Brook, 1991; Lowes et al, 1987)
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
