Characterization and Interconversion of Polymorphs of Premafloxacin, a New Quinolone Antibiotic

• Published in: Journal of pharmaceutical sciences 1997-12, Vol.86 (12), p.1426-1431
• Main Authors: Schinzer, W.C., Bergren, M.S., Aldrich, D.S., Chao, R.S., Dunn, M.J., Jeganathan, A., Madden, L.M.
• Format: Article
• Language: English
• Subjects: Anti-Infective Agents - chemistry; Biological and medical sciences; Calorimetry, Differential Scanning; Crystallization; Fluoroquinolones; General pharmacology; Medical sciences; Methanol; Pharmacology. Drug treatments; Physicochemical properties. Structure-activity relationships; Pyrroles - chemistry; Quinolones - chemistry; Solubility; Water; X-Ray Diffraction
• ISSN: 0022-3549; 1520-6017
• DOI: 10.1021/js970063o

□ The quinolone antibiotic premafloxacin crystallizes in at least five solid modifications, including three anhydrous phases (Forms I-III), a hydrate, and a methanolate. The anhydrous phases were studied by optical microscopy, X-ray powder diffraction, HPLC, hot-stage microscopy, dynamic moisture sorption gravimetry, differential scanning calorimetry, thermal gravimetry, and solution and isothermal calorimetry. Dry samples of Form I converted to Form II and ultimately to Form III through a sequence of melts and recrystallizations. Form III was stable to its melting temperature near 200 °C. Humidified samples of Form I converted directly to Form III via a moisture-mediated solid-state phase transformation at temperatures as low as 40 °C. The calorimetric and solubility data confirmed that Form III was lower in free energy and enthalpy than Form I at room temperature. Our investigation revealed that Form I was not crystallized directly from solution. Rather, Form I was the product of facile solid-state desolvation of the methanol solvate.