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

Recently, the synthesis and characterization of NTZ cocrystals using succinic, glutaric, 2,5-dihydroxybenzoic, p-aminobenzoic and p-aminosalicylic acid as coformers were reported [8, 44] . In both publications, improved intrinsic dissolution rates were documented, showing that NTZ cocrystals can improve the solubilization of NTZ in physiologically relevant media [8] , thus being good candidates for the future development of novel dosage forms. Herein, two cocrystals, viz., NTZ-GLU and NTZ-SUC (GLU = glutaric acid; SUC = succinic acid), were chosen to evaluate the effect of two cellulosic polymers, namely hydroxypropyl methylcellulose (HPMC) and methylcellulose (Methocel ® 60 HG) (Scheme 1), on the dissolution performance of the API, in comparison with pure NTZ, a commercially available NTZ medicine and the respective physical mixtures of NTZ and the coformer. Our study includes an API widely used in treatments concerning tropical neglected diseases, even though scarcely studied [45] . The purpose of this work was to study the behavior of NTZ cocrystals in solution and the conditions to sustain supersaturation levels since these conditions cannot be apparent and must be studied case-by-case. Given its therapeutic relevance, approaches to formulate nitazoxanide cocrystals will be of benefit to improve its efficacy, considering that its low solubility impacts its bioavailability. Importantly, nitazoxanide has been proposed as a potential agent for public health control [46] .