Influence of Temperature, Solvents, and Excipients on Crystal Transformation of Agomelatine

Agomelatine is a new and novel non-SSRI potential treatment option for major depressive disorders, discovered and developed by Servier Laboratories with first marketing approval in 2009. In this work, the solution-mediated crystal form I to II transformation process was studied. The influence factors, such as system temperature, crystallization solvents, and some pharmaceutical excipients, were investigated. DSC, XRPD, SEM, react IR, and in situ FBRM were used to monitor the transformation process. Compared with crystal form I of agomelatine, form II was the thermodynamic stable one, therefore, the transformation was a spontaneous process. By increasing the system temperature and/or the volume ratio of IPA in the solvent mixture, the transformation process would be accelerated. Lactose hydrate and HPMC would slightly inhibit the transformation, while PVP K30 would accelerate transformation process by increasing the solubility.