CHARACTERIZATION AND INTERCONVERSION OF POLYMORPHS OF PREMAFLOXACIN, A NEW QUINOLONE ANTIBIOTIC

The quinolone antibiotic premafloxacin crystallizes in al least five s olid modifications, including three anhydrous phases (Forms I-III), a hydrate, and a methanolate. The anhydrous phases were studied by optic al microscopy, X-ray powder diffraction, HPLC, hot-stage microscopy, d ynamic moisture sorption gravimetry, differential scanning calorimetry , thermal gravimetry, and solution and isothermal calorimetry, Dry sam ples of Form I converted to Form II and ultimately to Form III through a sequence of melts and recrystallizations. Form III was stable to it s melting temperature near 200 degrees C. Humidified samples of Form I converted directly to Form III via a moisture-mediated solid-state ph ase transformation at temperatures as low as 40 degrees C. The calorim etric and solubility data confirmed that Form III was lower in free en ergy and enthalpy than Form I at room temperature. Our investigation r evealed that Form I was not crystallized directly from solution. Rathe r, Form I was the product of facile solid-state desolvation of the met hanol solvate.