Characterization and interconversion of polymorphs of premafloxacin, a new quinolone antibiotic.
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 degrees 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 degrees 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.
Schinzer
W C
WC
Pharmacia and Upjohn, Kalamazoo, MI 49002, USA.
Bergren
M S
MS
Aldrich
D S
DS
Chao
R S
RS
Dunn
M J
MJ
Jeganathan
A
A
Madden
L M
LM
D000890:Anti-Infective Agents / Q000737:chemistry*; D002152:Calorimetry, Differential Scanning; D003460:Crystallization; D024841:Fluoroquinolones; D000432:Methanol; D011758:Pyrroles / Q000737:chemistry*; D015363:Quinolones / Q000737:chemistry*; D012995:Solubility; D014867:Water; D014961:X-Ray Diffraction
D000890:Anti-Infective Agents; D024841:Fluoroquinolones; D011758:Pyrroles; D015363:Quinolones; D014867:Water; C105016:premafloxacin; D000432:Methanol