RESUMO
An efficient protocol for assessing both the chemical and physical stability of cocrystalline forms of active pharmaceutical ingredients (APIs) is proposed. In this protocol, the cocrystalline material is used to prepare two standard formulations, mimicking wet granulations, to make low-dose tablets. After designed stress testing at a range of temperatures and RH conditions, degradant formation is modeled from the data using ASAPprime® to determine if the tablets have a minimum of a one-year shelf-life (25 °C/60% RH open). When the cocrystals provide a kinetic solubility enhancement over the un-complexed API, a physical assessment of the cocrystal stability is carried out using the same tablets at selected stress conditions. For this assessment, kinetic solubility (where the amount of buffer used to dissolve the tablet is adjusted to completely dissolve the cocrystalline form but leave most of the un-complexed form out of solution) changes are used to indicate whether there is a significant risk for physical instability on long-term storage. This process was exemplified using model cocrystals of APIs.