Enhancing Drug Delivery of Sparfloxacin Through Multicomponent Cocrystals and Sodium Taurocholate Additive

Cocrystal engineering has become ubiquitous in addressing the bioavailability challenges and solubility limitations posed by drugs falling under class II and IV of the Biopharmaceutical Classification System (BCS), such as sparfloxacin (BCS II), which exhibits poor water solubility and high permeability. In the present study, a new salt of sparfloxacin (SPX) with glutaric acid (GLU) in a 1:1 ratio was obtained to compare with previously reported 4-hydroxymethyl benzoate (MBZ) and 4-hydroxypropyl benzoate (PBZ) cocrystals. The incorporation of sodium taurocholate (STC), a bile salt known for its surfactant properties, into the dissolution medium of SPX cocrystals revealed intriguing insights into the role of STC in inhibiting phase transformation and enhancing solubility. Powder X-ray diffraction (PXRD), scanning electron microscopy (SEM), 1H NMR, and DSC provided further evidence that STC promotes the stability of SPX cocrystals during dissolution, thereby facilitating sustained supersaturation and improving drug permeability. Differential scanning calorimetry (DSC) particularly revealed that even low concentrations of STC inhibit the phase transformation of SPX-PBZ (1:1) cocrystal to SPX-PBZ-HYD. Equilibrium solubility showed the superior solubility of SPX cocrystals compared to the pure drug, with significant enhancement observed in the presence of STC, particularly SPX-GLU salt showing a 3.2-fold enhancement in the presence of STC (2 mg/mL) in pH 7 buffer media. The addition of STC resulted in varying degrees of dissolution and permeability enhancement across different cocrystals, with SPX-GLU salt showing the most pronounced improvement followed by SPX-PBZ, SPX-MBZ, and SPX, respectively. The normalized diffusion parameter (Diffnorm) of bioavailability was used as a metric to assess the true alterations in diffusion values of multicomponent solids. The results highlight the effectiveness of STC in improving the bioavailability of SPX cocrystals.