On the solid state conformation of azithromycin monohydrate and dihydrate pseudopolymorphs

Abstract

Abstract This paper describes the crystal structure of the azithromycin monohydrate pseudopolymorph (pseudopolymorphic forms, different solvates of the same chemical compound, azithromycin in our case) crystallised from isopropanol, solved by X-ray single crystal, and called isopropanol clathrate monohydrate (Apotex, US 6,245,903). The powder diffraction patterns for this compound show a structure very similar to the azithromycin monohydrate crystallised from ethanol, called stable monohydrate (Biochemie, WO 0100640), and the X-ray single crystal confirms the fact that this new pseudopolymorph is isostructural to the previously reported, the referred stable monohydrate. Comparing the monohydrate and the dihydrate crystalline forms, we try to explain the role played by the solvent in the final results, and find a relation between the conformation in solution and in the crystal state conformation for the antibiotic. The crystal obtained using t-butanol as solvent, differs from the expected and certainly more factors have to be considered in addition to the solvent polarity (dipole moment μ) to determine the final crystal form of azithromycin, contrary to that indicated in the literature. The concept of polarity itself is analyzed.