Dissolution Profile of Tosufloxacin Tosylate in Biorelevant Bicarbonate Buffer Containing Sodium Chloride: Precipitation of Hemi-hydrochloride Salt at the Particle Surface.

Purpose: 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 (pK: 5.8 and 8.7), formulated as tosylate salt to enhance its dissolution.

Methods: The dissolution profiles were measured in BCB or phosphate buffer (PPB) at pH 6.5 with buffer capacity (β) = 0.88 or 4.4 mM/pH, containing NaCl or NaSO (I = 0.14 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.

Results: TFLX TS dissolved less in the NaCl media than in the NaSO media. It also dissolved less in PPB than in BCB (at β = 4.4 mM/pH), and less at β = 4.4 mM/pH than at 0.88 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 NaSO media. The pH solubility profile matched the hemi-hydrochloride stoichiometry (K = [TFLX∙H][TFLX][Cl]).

Conclusion: 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.