AQUEOUS SOLUBILITIES OF SOME VARIOUSLY SUBSTITUTED QUINOLONE ANTIMICROBIALS

The fluorinated 4-quinolones are a group of orally active antimicrobials, which are active against a wide range of gram-negative organisms and gram-positive cocci. These compounds are essentially zwitterions at physiological pH and, therefore, in their lowest state of solubility. The objective of this study was to evaluate the solubility of a series of the fluoroquinolones as a function of pH, temperature, and salt concentration. The aqueous solubilities (μ = 0.15 with NaCI) at 25 and 37°C, the apparent macroscopic dissociation constants (μ = 0.15 with NaCl), and the melting points of a series of fluoroquinolone antimicrobials were determined. The intrinsic solubility (μ = 0.15 with NaCl) at 25°C for this group of compounds was found to range from 1.28 × 10-4 M (0.0297 mg ml-1) to 7.64 × 10-3 M (2.75 mg ml-1). At pH values between 5 and 7, if the solubility of quinolone was greater than 5 mg ml-1, the observed solubility was greater than that predicted by theory. At pH values below 5, there was evidence of the salt forms of the quinolones limiting the solubilities. The effect of NaCl on the solubility of lomefloxacin mesylate was studied and showed that increasing ionic strength may suppress the solubility more than could be explained by the common-ion effect alone. The apparent macroscopic dissociation constants (μ = 0.15 with NaCl) were found to range from 5.46 to 6.30 for the carboxylic acid function. The range of apparent macroscopic dissociation constants for the piperazinyl function was found to be 9.0 ± 0.3 for all compounds except those with a methyl substituent on the piperazinyl nitrogen, in which case, the range was 7.8 ± 0.4. © 1990.