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 use of excipients such as polymers and surfactants constitutes an efficient strategy to prolong drug supersaturation achieved from pharmaceutical cocrystals [23] [24] [25] 36, 57 ]. An addition of a cellulosic polymer into the dissolution medium for powder dissolution studies under non-sink conditions revealed that these can induce a supersaturation effect starting from NTZ-SUC and NTZ-GLU cocrystals. Both Methocel ® 60 HG and HPMC were able to maintain drug supersaturation (up to 4 times higher concentrations of NTZ in solution over solubility value) for a period long enough to display a superior dissolution profile (Figure 2b,c) . The phenomenon was upheld for up to 30 min, emulating the spring-parachute effect [48] . There are some studies demonstrating an in vitro/in vivo correlation of formulated cocrystals. In these cases, the in vitro dissolution test showed that the high drug concentration achieved by cocrystalline phases is maintained by 30-40 min and the bioavailability of the corresponding poorly soluble drugs was enhanced [24, 33] . Considering these experimental data, it is considered that the increase of NTZ dissolved from NTZ cocrystals formulated with polymers may promote NTZ absorption.