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

The cocrystal solubilization can be quantified by the AUC (area under the curve), thus constituting a parameter indicative of the influence that cocrystals have on the API performance. The AUC is directly and inversely proportional to the dissolution and precipitation rates, respectively [49] . Figure 7 shows that unformulated NTZ-SUC cocrystals and NTZ-SUC formulated with 1.0% w/w Methocel ® 60 HG do not lead to improved dissolution profiles when compared to NTZ and the physical mixture of NTZ and SUC (p > 0.05). However, for the formulations with 2.5 and 5.0% (w/w) of polymer, the AUC for the NTZ-SUC cocrystal increased by factors of 8.0 and 9.2, respectively, in comparison to the unformulated NTZ. Meanwhile, for NTZ and the physical mixture with SUC the AUC are practically constant in the polymer formulations examined herein. Selected samples of the solid residues recovered after the dissolution tests were analyzed by PXRD and SEM analysis. The PXRD data showed that the NTZ-SUC cocrystal is transformed into its parent drug in all of the formulations tested (Figure 8) , and it was also observed in the dissolution experiments under non-sink conditions. Peaks for SUC are not observed, indicating that the coformer was completely dissolved, which is in agreement with its good solubility in water (71 mg/mL at 25 °C). Selected samples of the solid residues recovered after the dissolution tests were analyzed by PXRD and SEM analysis. The PXRD data showed that the NTZ-SUC cocrystal is transformed into its parent drug in all of the formulations tested (Figure 8) , and it was also observed in the dissolution experiments under non-sink conditions. Peaks for SUC are not observed, indicating that the coformer was completely dissolved, which is in agreement with its good solubility in water (71 mg/mL at 25 • C).