Solid-State Hydration/Dehydration of Erythromycin A Investigated by ab Initio Powder X‑ray Diffraction Analysis: Stoichiometric and Nonstoichiometric Dehydrated Hydrate

The stable dihydrate crystalline phase (<b>DH</b>) of erythromycin A loses water upon heating to give the anhydrous phase I (<b>AI</b>). Further heating then results in a polymorphic transformation via the amorphous state (melt) to give another anhydrous phase II (<b>AII</b>). The anhydrous phases of <b>AI</b> and <b>AII</b> undergo hydration when increasing the humidity. The crystals of <b>AI</b> showed stoichiometric hydration to give <b>DH</b>, whereas the crystals of <b>AII</b> showed nonstoichiometric hydration to give the humidity dependent nonstoichiometric hydrate phase (<b>NSH</b>). The crystal structures of <b>AI</b> and <b>AII</b> were directly determined from powder X-ray diffraction data using the direct space strategy for the structure solution followed by Rietveld refinement. From the structural properties of <b>AI</b> and <b>AII</b>, aspects of the mechanism of the solid-state transformations of <b>DH</b> and the hydration behavior of <b>AI</b> and <b>AII</b> have been determined, and the importance of the hydrophilicity of the voids has been revealed