Thermoanalytical studies of carbamazepine: hydration/dehydration, thermal decomposition, and solid phase transitions

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. Uniterms:Carbamazepine/thermal analysis. Polymorphism. Hydrate. Dehydration.A carbamazepina (CBZ) é um anticonvulsivante frequentemente utilizado no Brasil e em vários países. Ela apresenta quatro formas polimórficas e um diidrato. Todas as formas são ativas farmacologicamente, porém a Forma III é a preferível do ponto de vista farmacêutico, em função de suas propriedades físico-químicas. Entretanto, essa forma é altamente higroscópica, podendo converter-se ao diidrato, menos ativo biologicamente. Nesse trabalho propõe-se avaliar o comportamento térmico da forma hidratada, visando à recuperação da forma ativa, por aquecimento. Para tanto, foi feito um estudo do comportamento térmico por TG/DTG-DTA e DSC em atmosfera dinâmica de ar e nitrogênio, que evidenciou hidratação espontânea da Forma III, gerando um hidrato contendo 1,5 moléculas de água. Essa forma sofre desidratação, seguida de fusão e conversão para a Forma I. Segue-se a decomposição em uma única etapa, na qual ocorre liberação do ácido isociânico, conforme análise de gases evolvidos, por termogravimetria acoplada ao infravermelho (TG-FTIR). Estudos por calorimetria exploratória diferencial mostraram que a Forma III se funde e se cristaliza imediatamente na Forma I, durante o aquecimento. A Forma I também se funde e ciclos de aquecimento/resfriamento posteriores evidenciaram que a substância se cristaliza apenas na Forma I por resfriamento. Estudos cinéticos da decomposição, em estado sólido, mostraram que não há alteração na substância pela eliminação da água por aquecimento, sendo determinados valores de energia de ativação da ordem de 98 ± 2 e 93 ± 2 kJ mol -1 , respectivamente, para a amostra hidratada e submeti...

Specific adsorption sites and conditions derived by thermal decomposition of activated carbons and adsorbed carbamazepine

“…2 and Table S1). As a result, we determined activation energies of 92 ± 2 kJ mol −1 for SAE+CBZ-15 and 92 ± 3 kJ mol −1 for HK+CBZ-15 very close to 93 ± 2 kJ mol −1 for pure carbamazepine (Table S2) 43 . In conclusion, no catalytic effects seem to be at play.…”

“…Isocyanic acid is a likely leaving group of carbamazepine. Furthermore, the elimination of isocyanic acid during the thermal decomposition of pure carbamazepine has been previously described by Pinto et al 43 We conducted experiments on decomposition kinetics for SAE+CBZ-15 and HK+CBZ-15, to investigate catalytic effects that may cause the observed temperature shift for the elimination of isocyanic acid in the 1 st decomposition stages ( Fig. 2 and Table S1).…”

Pharmaceutical Hydrates Analysis—Overview of Methods and Recent Advances

“…Many more far reaching structural consequences can cause dehydration in a hydrate co-crystal. Water loss from carbamazepine-nicotinamide cocrystal hydrate induced new co-crystallization between anhydrous carbamazepine and nicotinamide [ 141 ], ending up in a completely new structure. All the changes have been observed thanks to step by step PXRD analysis.…”

Synthesis and release behavior of layered double hydroxides – carbamazepine composites

“…In the LDH-CBZ sample, the total weight loss was only 45 %; this difference is due to the absence of SC. In the sample synthetized by reconstruction, it can be observed by DTG analyses that the first thermal event, occurred between 70-80 °C, correspond to the CBZ dehydration 24 ; the transitions observed up to 170 °C are associated with the removal of the interlayer water. Finally, the last transition corresponds to SC decomposition 25 .…”

“…By literature, the decomposition of pure CBZ begins at 200 °C 24 ; in DTG diagrams the decomposition is not observed until 300 °C, which can be associated with the superficial CBZ observed in LDH-CBZ-SC60 by XRD. From 350 °C, the decomposition of the sheets is observed; the dihydroxylation of the lamella, decomposition and combustion of the intercalated CBZ occur together.…”