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

Previous formulations with cocrystals were based on polymer matrix tablets [29, 30] and pre-dissolved polymers [24, 36] . However, there are few studies which have tested the effect of a polymer incorporated in the powder solid-state form on the dissolution profiles of cocrystals [23] . In order to evaluate the effect of Methocel ® 60 HG on the dissolution process of NTZ-SUC cocrystals starting from a solid polymer-cocrystal formulation, we examined a series of pharmaceutical powder-based formulations containing different amounts of Methocel ® 60 HG (0.0, 1.0, 2.5 and 5.0% w/w) in comparison to analogous forms with pure NTZ and the physical mixture of NTZ and SUC. In the absence of polymer, all solid phases released similar amounts of NTZ into the solution during the powder dissolution studies using the USP 1 apparatus (Figure 6a ) and the NTZ-SUC cocrystal did not show a solubility advantage in comparison with the pure drug and the physical mixture. This observation can be attributed to immediate conversion of the cocrystal phase into NTZ and release of SUC into the solution, in accordance with the dissolution experiments under non-sink conditions. Formulations of pure NTZ, the physical mixture with SUC, and NTZ-SUC cocrystals with 1% (w/w) of Methocel ® 60 HG showed dissolution profiles being similar among each other, but at higher concentrations, i.e., 2.5 and 5.0% (w/w), a significant increase of the dissolution rate was observed (Figure 6c ,d and Figure 7) .