Fig. 5. Calculated free-energy versus relative-humidity curves of form III (anhydrate), form I (hemihydrate) and the predicted rank 1 monohydrate of upadacitinib at 25 °C.

The rank 1 monohydrate is predicted to be unstable for the entire humidity range. The 1σ confidence interval on the relative humidity at coexistence between form I and form III is shown beneath the free-energy curves. The experimental transition is observed at 14% relative humidity at 25 °C.