title: Very fast dissolving acid carboxymethylcellulose-rifampicin matrix: Development and solid-state characterization.
abstract: One of the main obstacles to the successful treatment of tuberculosis is the poor and variable oral bioavailability of rifampicin (RIF), which is mainly due to its low hydrophilicity and dissolution rate. The aim of this work was to obtain a hydrophilic new material that allows a very fast dissolution rate of RIF and therefore is potentially useful in the development of oral solid dosage forms. The acid form of carboxymethylcellulose (CMC) was co-processed with RIF by solvent impregnation to obtain CMC-RIF powder, which was characterized by polarized optical microscopy, powder x-ray diffraction, DSC-TGA, hot stage microscopy,13C and15N solid-state NMR and FT-IR spectroscopy. In addition, the CMC-RIF matrices were subjected to water uptake and dissolution studies to assess hydrophilicity and release kinetics. CMC-RIF is a crystalline solid dispersion. Solid-state characterization indicated that no ionic interaction occurred between the components, but RIF crystallized as a zwitterion over the surface of CMC, which drastically increased the hydrophilicity of the solid. The CMC-RIF matrices significantly improved the water uptake of RIF and disintegrated in a very short period immediately releasing RIF. As CMC improves the hydrophilicity and delivery properties of RIF, CMC-RIF is very useful in the design of oral solid dosage forms with very fast dissolution of RIF, either alone or in combination with other antitubercular drugs.
authors.affiliation: Unidad de Investigación y Desarrollo en Tecnología Farmacéutica (UNITEFA), CONICET and Departamento de Farmacia, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Ciudad Universitaria, 5000 Córdoba, Argentina.
authors.forename: Laura C
authors.initials: LC
authors.lastname: Luciani-Giacobbe
authors.affiliation: Planta Piloto de Ingeniería Química (PLAPIQUI), CONICET and Departamento de Ingeniería Química, Universidad Nacional del Sur, Camino La Carrindanga Km 7, 8000 Bahía Blanca, Argentina; Departamento de Biología, Bioquímica y Farmacia, Universidad Nacional del Sur, San Juan 670, 8000 Bahía Blanca, Argentina.
authors.forename: María V
authors.initials: MV
authors.lastname: Ramírez-Rigo
authors.affiliation: Instituto de Física Enrique Gaviola (IFEG), CONICET and Facultad de Matemática, Astronomía y Física, Universidad Nacional de Córdoba, Ciudad Universitaria, 5000 Córdoba, Argentina.
authors.forename: Yamila
authors.initials: Y
authors.lastname: Garro-Linck
authors.affiliation: Instituto de Física Enrique Gaviola (IFEG), CONICET and Facultad de Matemática, Astronomía y Física, Universidad Nacional de Córdoba, Ciudad Universitaria, 5000 Córdoba, Argentina.
authors.forename: Gustavo A
authors.initials: GA
authors.lastname: Monti
authors.affiliation: Unidad de Investigación y Desarrollo en Tecnología Farmacéutica (UNITEFA), CONICET and Departamento de Farmacia, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Ciudad Universitaria, 5000 Córdoba, Argentina.
authors.forename: Ruben H
authors.initials: RH
authors.lastname: Manzo
authors.affiliation: Unidad de Investigación y Desarrollo en Tecnología Farmacéutica (UNITEFA), CONICET and Departamento de Farmacia, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Ciudad Universitaria, 5000 Córdoba, Argentina. Electronic address: meoliver@fcq.unc.edu.ar.
authors.forename: María E
authors.initials: ME
authors.lastname: Olivera
mesh_terms: D002152:Calorimetry, Differential Scanning / Q000379:methods; D002266:Carboxymethylcellulose Sodium / Q000032:analysis* / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D012293:Rifampin / Q000032:analysis* / Q000737:chemistry*; D012995:Solubility; D017550:Spectroscopy, Fourier Transform Infrared / Q000379:methods; D013997:Time Factors; D014961:X-Ray Diffraction / Q000379:methods
chemical_list: D002266:Carboxymethylcellulose Sodium; D012293:Rifampin
keywords: Crystalline solid dispersion; Dissolution rate; Drug delivery; Rifampicin; Solid-state properties; Wetting; Zwitterion