Enhancing Drug Delivery of Sparfloxacin Through Multicomponent\nCocrystals and Sodium Taurocholate Additive

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