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Open AccessArticle

Dissolution Advantage of Nitazoxanide Cocrystals in the Presence of Cellulosic Polymers

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Facultad de Farmacia, Universidad Autónoma del Estado de Morelos, Av. Universidad 1001, Cuernavaca 62209, Mexico
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Centro de Investigaciones Químicas, Instituto de Investigación en Ciencias Básicas y Aplicadas, Universidad Autónoma del Estado de Morelos, Av. Universidad 1001, Cuernavaca 62209, Mexico
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Departamento de Ingeniería Química, Universidad Politécnica de Tlaxcala, Carretera Federal Tlaxcala-Puebla Km 9.5, Tepeyanco, Tlaxcala 90180, Mexico
*
Authors to whom correspondence should be addressed.
Pharmaceutics 2020, 12(1), 23; https://doi.org/10.3390/pharmaceutics12010023
Received: 22 November 2019 / Revised: 19 December 2019 / Accepted: 22 December 2019 / Published: 25 December 2019
(This article belongs to the Special Issue Cocrystal Applications in Drug Delivery)
The effect of hydroxypropyl methylcellulose (HPMC) and methylcellulose (Methocel® 60 HG) on the dissolution behavior of two cocrystals derived from nitazoxanide (NTZ), viz., nitazoxanide-glutaric acid (NTZ-GLU, 1:1) and nitazoxanide-succinic acid (NTZ-SUC, 2:1), was explored. Powder dissolution experiments under non-sink conditions showed similar dissolution profiles for the cocrystals and pure NTZ. However, pre-dissolved cellulosic polymer in the phosphate dissolution medium (pH 7.5) modified the dissolution profile of NTZ when starting from the cocrystals, achieving transient drug supersaturation. Subsequent dissolution studies under sink conditions of polymer-based pharmaceutical powder formulations with NTZ-SUC cocrystals gave a significant improvement of the apparent solubility of NTZ when compared with analogous formulations of pure NTZ and the physical mixture of NTZ and SUC. Scanning electron microscopy and powder X-ray diffraction analysis of samples recovered after the powder dissolution studies showed that the cocrystals undergo fast dissolution, drug supersaturation and precipitation both in the absence and presence of polymer, suggesting that the solubilization enhancement is due to polymer-induced delay of nucleation and crystal growth of the less soluble NTZ form. The study demonstrates that the incorporation of an appropriate excipient in adequate concentration can be a key factor for inducing and maintaining the solubilization of poorly soluble drugs starting from co-crystallized solid forms. In such a way, cocrystals can be suitable for the development of solid dosage forms with improved bioavailability and efficacy in the treatment of important parasitic and viral diseases, among others. View Full-Text
Keywords: nitazoxanide; cocrystals; multicomponent crystals; dissolution behavior; supersaturated formulations; crystallization inhibitors; drug-polymer interactions nitazoxanide; cocrystals; multicomponent crystals; dissolution behavior; supersaturated formulations; crystallization inhibitors; drug-polymer interactions
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Salas-Zúñiga, R.; Rodríguez-Ruiz, C.; Höpfl, H.; Morales-Rojas, H.; Sánchez-Guadarrama, O.; Rodríguez-Cuamatzi, P.; Herrera-Ruiz, D. Dissolution Advantage of Nitazoxanide Cocrystals in the Presence of Cellulosic Polymers. Pharmaceutics 2020, 12, 23.

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