Using Co-crystals to Alter Physicochemical Properties of APIs

5 Using Co-crystals to Alter Physicochemical Properties of APIs 

A variety of reports are available on co-crystals that have been subjected to different stability conditions including, relative humidity, thermal, chemical, solution and thermodynamic. For potential co-crystal candidates, each of these conditions should be tested and the information gained should be used to evaluate and design processing conditions, scale-up, formulations, packaging, and so on. 

Solution stability is a very important parameter to assess during development and for this discussion will be defined as the ability of the co-crystal components to stay in solution and not readily crystallize or precipitate. A variety of media can be introduced, including water, simulated gastric fluid (SGF), simulated intestinal fluid (SIF), formulation vehicles, and buffered solutions. In many instances, these experiments can be coupled with solubility or dissolution experiments to obtain a more complete picture of the behavior and the solid form remaining at the end of the experiment. Because dissociation of a cocrystal often occurs and precipitation of a less soluble form (either one of the components or another co-crystal) can result, solution stability studies should be considered early in development of a potential drug product. Attention has been focused on formulation approaches to stabilize the co-crystal (or cocrystal components) in solution by addition of surfactants to avoid the problem of recrystallization. One of the first reports on this approach was published by Remenar et al. on a celecoxibmicotinamide co-crystal in various formulation vehicles (110% sodium dodecylsulfate (SDS) and polyvinylpyrrolidone (PVP)) in order to understand the solid form that may result upon contact with 

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