The effect of temperature and pH on the solubility of quinolone compounds: estimation of heat of fusion

Pharm Res. 1994 Apr;11(4):522-7. doi: 10.1023/a:1018910431216.


Although many reports involving fluoroquinolone agents have been published in the past decades, only a few address preformulation studies. In this paper, we describe the effect of temperature and pH on the aqueous solubility of two typically used quinolones, ciprofloxacin and norfloxacin. We measured the aqueous solubilities over the pH range of 5.5 to 9.5 at temperature of 6, 25, 30, and 40 degrees C. The intrinsic solubilities and the thermodynamic dissociation constants were determined from solubility data and the temperature dependence of the intrinsic solubility was evaluated using van't Hoff and Hildebrand plots. The heat of fusion was determined from these two plots. When the heat of fusion was compared to that measured from differential scanning calorimetry (DSC) studies, we found that the Hildebrand method overestimated, and the van't Hoff equation underestimated, the heat of fusion. From the absolute values of the relative errors, the Hildebrand plot produced the better results. DSC results show that the heat of fusion is 15.41 kcal/mol for ciprofloxacin and 7.88 kcal/mol for norfloxacin.

MeSH terms

  • Calorimetry, Differential Scanning
  • Chromatography, High Pressure Liquid
  • Ciprofloxacin / chemistry
  • Hot Temperature
  • Hydrogen-Ion Concentration
  • Norfloxacin / chemistry
  • Quinolones / chemistry*
  • Solubility
  • Temperature
  • Thermodynamics


  • Quinolones
  • Ciprofloxacin
  • Norfloxacin