Dissolution Advantage of Nitazoxanide Cocrystals in the Presence of Cellulosic Polymers

Salas-Zúñiga, Reynaldo; Rodríguez-Ruiz, Christian; Höpfl, Herbert; Morales-Rojas, Hugo; Sánchez-Guadarrama, Obdulia; Rodríguez-Cuamatzi, Patricia; Herrera-Ruiz, Dea

NTZ was combined with GLU and SUC in 1:1 and 2:1 stoichiometric ratio, respectively, using the liquid-assisted grinding method with acetone as solvent as previously reported [8] . NTZ-SUC and NTZ-GLU cocrystals were prepared in scales of 1.0 g, and in all cases a homogeneous single phase was obtained, for which the experimental PXRD pattern agreed with the pattern simulated from the crystal structure determined by single-crystal X-ray diffraction analysis (see Figure S4 ). A batch of ten (individually characterized) samples was finally mixed and used for all subsequent experiments. Figure 1 shows the effect of polymers commonly employed in pharmaceutical drug formulations to inhibiting or delaying precipitation of NTZ. In the absence of polymers, addition of aliquots from NTZ stock solution (25 mg/mL) to 3 mL of a phosphate buffer solution (PBS, pH 7.5) caused precipitation of NTZ at concentrations above 0.30 mg/mL. In the presence of 0.5% w/v pre-dissolved cellulosic polymers, i.e., Methocel ® MC, Methocel ® 60 HG, HMPC, HPC 80,000 and HPC 370,000, as well as the polyvinylpyrrolidone Kollidon ® 25, precipitation of NTZ was inhibited, reaching concentrations of at least 1.0 mg/mL; meanwhile, polyethylene glycol Kollisolv ® and poloxamer Kolliphor ® P 407 maintained the drug dissolved only at concentrations below 0.25-0.40 mg/mL. Based on these results, HPMC and Methocel ® 60 HG were selected for subsequent powder dissolution experiments of NTZ and the cocrystal phases with GLU and SUC under non-sink conditions. Pharmaceutics 2020, 12, x 6 of 18 on these results, HPMC and Methocel ® 60 HG were selected for subsequent powder dissolution experiments of NTZ and the cocrystal phases with GLU and SUC under non-sink conditions.