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

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.

卡马西平（Carbamazepine，简称CBZ）是一种临床广泛应用的抗惊厥药物，可发生结晶，且存在四种多晶型与一种二水合物形式。无水CBZ可自发吸收水分并转化为水合物形式，不同结晶度的该水合物生物活性更低。本研究聚焦于通过加热回收该水合形式的可行性。研究采用TG/DTG-DTA与差示扫描量热法（DSC），在空气与氮气动态气氛下对自发水合卡马西平的热行为进行了探究，结果显示该药物的自发水合产物为含1.5个水分子的Ⅲ型水合物。经脱水后，该无水Ⅲ型会转化为Ⅰ型，后者将在单一过程中熔融并分解，释放异氰酸，该结论通过采用TG-FTIR的逸出气体分析得以证实。差示扫描量热分析结果表明，Ⅲ型会熔融并结晶为Ⅰ型，且后续的冷却循环仅能通过结晶生成Ⅰ型。固态分解动力学研究显示，将样品加热至120℃脱除水分后，其物质组成未发生改变。研究测得水合样品与干燥样品的活化能分别为98±2 kJ·mol⁻¹与93±2 kJ·mol⁻¹，且二者的活化能随转化因子变化的曲线轮廓相似。