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 Figure 6a illustrates the dissolution profiles measured over a time interval of 3 h of the unformulated (0.0% w/w of Methocel ® 60 HG) solid phases of pure NTZ, the physical mixture with SUC and the NTZ-SUC cocrystal. The drug dissolution profiles are similar (p > 0.05), achieving approximately 8 mg of dissolved drug (ca. 3% in relation to 250 mg of NTZ dose). In contrast, when the solid phases were formulated with 1.0% Methocel ® 60 HG, the drug was dissolved in significantly larger amounts, either starting from the pure form, the physical mixture or the cocrystal (~17-27 mg of drug dissolved after 3 h). Although the graph associated to NTZ-SUC exhibits a larger increase, the statistical difference (p > 0.05) between the dissociation rates is not significant due to the relatively large standard deviation (Figure 6b ). However, with larger amounts of Methocel ® 60 HG polymer (2.5 and 5.0%), the NTZ-SUC cocrystal gave a significantly improved dissolution profile (p < 0.05) when compared to analogous formulations of pure NTZ and the physical mixture, achieving after 3 h, amounts of 42 and 45 mg of NTZ dissolved (Figure 6c,d) . Furthermore, for the formulation of the cocrystal with 5% Methocel ® 60 HG, the amount of NTZ dissolved after 2 min was already approximately 12 mg (Figure 6d ), which is significantly larger than the final amount achieved by the corresponding unformulated solid phases (Figure 6a) .