Roflumilast – A reversible single-crystal to single-crystal phase transition at 50 °C

Roflumilast is a selective phosphodiesterase type 4 inhibitor and is marketed under the brand names Daxas®, Daliresp® and Libertec®. A phase transition of the drug substance roflumilast was observed at 50 °C. The low temperature form, the high temperature form and the phase transition were characterised by differential scanning calorimetry, variable temperature powder X-ray diffraction and single crystal X-ray diffraction, Raman spectroscopy and solid state NMR spectroscopy.The phase transition of roflumilast at 50 °C is completely reversible, the high temperature form cannot be stabilised by quench cooling and the phase transition does not influence the quality of the active pharmaceutical ingredient (API) and the drug product. It was observed to be a single crystal to single crystal phase transition.

► Crystalline roflumilast shows a completely reversible phase transition at 50 °C.
► The phase transition was observed to be a single crystal to single crystal phase transition.
► The high temperature form cannot be stabilised at lower temperatures by quench cooling.
► The quality of the API and the drug product is not affected by the phase transition.