Purpose <p>The purpose of the present study was to investigate the dissolution profile of tosufloxacin tosylate monohydrate (TFLX TS) in biorelevant bicarbonate buffer (BCB). TFLX is a zwitterionic drug (p<i>K</i>_<i>a</i>: 5.8 and 8.7), formulated as tosylate salt to enhance its dissolution.</p> Methods <p>The dissolution profiles were measured in BCB or phosphate buffer (PPB) at pH 6.5 with buffer capacity (β) = 0.88 or 4.4&#xa0;mM/pH, containing NaCl or Na₂SO₄ (<i>I</i> = 0.14&#xa0;M). The residual particles were analyzed by powder X-ray diffraction. In a separate study, the particle surface of TFLX TS after contact with BCB was observed by scanning electron microscopy and real-time polarized light microscopy. The pH solubility profile of TFLX was measured using HCl and TS solutions.</p> Results <p>TFLX TS dissolved less in the NaCl media than in the Na₂SO₄ media. It also dissolved less in PPB than in BCB (at β = 4.4&#xa0;mM/pH), and less at β = 4.4&#xa0;mM/pH than at 0.88&#xa0;mM/pH. The analysis of residual particles indicated that the hemi-hydrochloride salt (TFLX 1/2HCl) precipitated on the particle surface of TFLX TS in the NaCl media. In contrast, the free form of TFLX precipitated in the Na₂SO₄ media. The pH solubility profile matched the hemi-hydrochloride stoichiometry (<i>K</i>_<i>sp</i> = [TFLX∙H⁺][TFLX][Cl⁻]).</p> Conclusion <p>The dissolution of TFLX TS in the NaCl media was suppressed by the precipitation of TFLX 1/2HCl on the particle surface. This is an important case showing that NaCl can suppress the dissolution profile of a non-HCl drug salt at a neutral pH.</p>