Structural and vibrational characterization of Azithromycin Hydrates

La Plata

Encuentro; Reunión Nacional de Cristalografía; 2005

Asociación Argentina de Cristalografía (AACr)

Polymorphism and pseudopolymorphism are important solid state properties that influence the performance and processing of solid dosage forms. Pseudopolymorphism deals with different solvates of the same chemical compound, being hydrates the most common solvate in pharmaceutical compounds. Hydrates of drug can influence physicochemical properties, processing, mechanical, compaction behavior etc. In addition, water in hydrates can also influence the intermolecular interactions, crystalline disorder, solubility, dissolution rate, higroscopicity, stability and bioavailability. Therefore, characterization of solid state properties at an early stage using appropriate analytical methodology is an essential prerequisite in the development of solid dosage forms. Azithromycin1-3 (AZI) is a semisynthetic acid-stable erythromycin derivative with an expanded spectrum of activity and improved pharmacokinetic characteristics. The commercial form is dihydrate; however, AZI raw materials from different manufacturers were found to exhibit variable solid state behavior (PXRD, FT-IR). At present, two of the most powerful techniques for the structural characterization of APIs (active pharmaceutical ingredients) are X-ray diffraction and vibrational spectroscopy, since they give directly precise structural and molecular information. The aim of this presentation is to report the difference in the crystal structure between dihydrate and monohydrate of AZI an our results give rise to a precise determination of the crystal structure as well as the vibrational spectra of AZI monohydrate. 1- S. Djokic et al, J. Chem. Soc., Perkin Trans. 1, 1881 (1986) 2- S. Djokic et al, J. Chem. Res. (S) 152 (1988), J. Chem. Res. (M) 1239 (1988) 3- R. Gandhi et al, Eur. J. Pharm. Sci. 16, 175-184 (2001)