Different Dissolution Molecular Pathways of Azilsartan Crystals with Different Forms Revealed by In Situ Atomic Force Microscopy.

Here, using in situ atomic force microscopy (AFM), the dissolution behaviors and dissolution molecular pathways of two azilsartan crystals, the isopropanol solvate (AZ-IPA), and form I (AZ-I), in pure water and 6-30% poly(ethylene glycol) (PEG) aqueous solutions are revealed. The dissolution behaviors of step retreat and etch pit formation are observed on the (100) faces of the two crystals, with a single step corresponding to one molecular monolayer in crystal structures. Etching rates of pits increase with PEG concentration. Furthermore, our results show that AZ-IPA dissolves by the direct detachment of molecules from the step front to solution. Such a mechanism remains even when the PEG concentration changes. However, AZ-I dissolves primarily by the surface diffusion mechanism involving molecular detachment from the step front at first and then diffusion over the terraces before desorption into solution. PEG promotes the dissolution of AZ-I crystals by favoring the molecular detachment from the step front.