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

Abstract

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.

Classical Spiral Growth Mechanism of Azilsartan Form I Revealed by In Situ Atomic Force Microscopy

“…AZ crystals grown from ethanol solutions exhibit a hexagonal, plate-like habit (Figure S1). The crystal is characterized to be form I (AZ-I) by PXRD (Figure S2), consistent with the previous reports. , The PXRD pattern of bulk crystals shows the dominance of the (100) face in bulk crystal morphology, which is also confirmed by single-crystal X-ray diffraction. Face indexing reveals that the upward face is the (100) face, flanked by the {001} and {011} faces (Figure a).…”

Solvates and Polymorphs of Baloxavir Marboxil: Crystal Structure and Phase Transformation Study

“…In the pharmaceutical field, polymorphism is defined as crystalline active pharmaceutical ingredients (APIs) with the same chemical composition but different arrangements and/or different molecular conformations . Different crystal forms may possess different physicochemical properties such as density, − flowability, solubility, − permeability, and stability, , which will further affect the selection of downstream processing technology and bioavailability. During the process of polymorphic screening, solvates are sometimes obtained easily. , Although most of solvates containing toxic solvents cannot be used in drug production, new crystal forms may only be obtained through desolvation. − Besides, phase transformations such as metastable crystal transformation − and solvate desolvation , may occur in the production and storage stages, which cause the drug to lose its effectiveness or even threaten human life. , Therefore, to obtain new solid forms of APIs with excellent performance and to avoid undesired phase transitions, it is crucial to obtain more information about the solid forms through polymorphic screening and investigation of the phase transformation process. , …”