Insight into the role of hydrochloric acid in the thermodynamics and nucleation kinetics behavior of Arbidol hydrochloride monohydrate from Metastable Zone Widths

In order to investigate the nucleation behavior of arbidol hydrochloride monohydrate (AHM) in the aqueous THF (Tetrahydrofuran) solutions, metastable zone width (MSZW) was experimentally determined via the polythermal method, and then modified Sangwal’s theory was employed to explain the nucleation process. Via the MSZW investigation, the existence of hydrochloric acid might contribute to the nuleation of the AHM from the crystallization mother liquor, which accords with our previous experiment result that it is vital to manufacture AHM in a solvent system with hydrochloric acid. Based on the classic nucleation theory, modified Sangwal’s theory was also employed to estimate the solid-liquid interfacial tension, critical nucleus size and the nucleation Gibbs energy, severally. Moreover, it is also proved that the solid-liquid interfacial tension not only reliance on temperature, but also on nucleation driving force. The surface roughness factor fr was estimated to imply the occurrence of continuous growth at the crystal interface of AHM in aqueous THF solutions. Finally, the comparisons of the calculated and experimental induction time indicate that Kubota theory has a high applicability for AHM in the aqueous THF system.