One-phase crystal disorder in pharmaceutical solids and its implication for solid-state stability.

Solid-state disorders of active pharmaceutical ingredients have been characterized by means of X-ray diffraction techniques and solid-state nuclear magnetic resonance spectroscopy. The results determined that the pleuromutilin-derivative, I, displays a unique continuous conformational disorder while retaining its long-range crystalline structure. The propionic acid (PA) version of this compound displayed partial crystalline order and site disorder of PA, depending on the quantity of PA incorporated in the structure. Thus, I is a unique example of one-phase crystalline-amorphous model. Physical and chemical stability data was acquired on these disordered systems and discussed in relation with the characterized disorder present in the crystal systems. Analysis of the results showed that in contrast to phase-separated amorphous, restrained disorders do not influence the stability.