title: Reduced food interaction and enhanced gastrointestinal tolerability of a new system based on risedronate complexed with Eudragit E100: Mechanistic approaches from in vitro and in vivo studies.
abstract: Novel complexes consisting of Eudragit E100-risedronate are presented. The oral bioavailability of risedronate in rats was determined through its percentage excreted in urine after administration of complexed or free risedronate in fed and fasted conditions. The evaluation of the risedronate gastro-duodenal irritation potential was carried out by macroscopic and histological analyses in an experimental rat model. The degree of counterionic condensation between Eudragit E100 and risedronate was assessed by dialysis with, mechanistic information about the interaction with calcium and the release of risedronate from the complexes being obtained using physiological solution and simulated gastric fluid without pepsin. Non-significant differences were observed in the urinary excretion of risedronate when the complex or free risedronate was administered to fasted rats. However, the urinary excretion of risedronate in the complex group was 4-times higher than in the free risedronate group when animals were concomitantly administered with food. This behavior was related to the high degree of counterionic condensation in the complex (86.5%), which led to a reduction in the calcium induced rate and magnitude of risedronate precipitation and resulted in a decrease in the gastroduodenal damage from the complex, as evidenced by a lower frequency of gastric mucosae hemorrhage. A sustained release of risedronate from the complex was observed toward water, simulated gastric fluid or physiological solution, through an ionic-exchange mechanism. In conclusion, complexation with Eudragit E100 could be a useful strategy to overcome the unfavorable properties of risedronate.
authors.affiliation: Unidad de Investigación y Desarrollo en Tecnología Farmacéutica (UNITEFA), CONICET and Departamento de Farmacia, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Argentina.
authors.forename: M L
authors.initials: ML
authors.lastname: Guzman
authors.affiliation: Instituto de Investigaciones en Ciencias de la Salud (INICSA), CONICET and Facultad de Ciencias Médicas, Universidad Nacional de Córdoba, Argentina.
authors.forename: E A
authors.initials: EA
authors.lastname: Soria
authors.affiliation: Instituto de Biotecnología, Centro de Investigación e Innovación Tecnológica de la Facultad de Ciencias Exactas Físicas y Naturales, Universidad Nacional de la Rioja, Argentina.
authors.forename: C
authors.initials: C
authors.lastname: Laino
authors.affiliation: Unidad de Investigación y Desarrollo en Tecnología Farmacéutica (UNITEFA), CONICET and Departamento de Farmacia, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Argentina.
authors.forename: R 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, Argentina. Electronic address: meoliver@fcq.unc.edu.ar.
authors.forename: M E
authors.initials: ME
authors.lastname: Olivera
mesh_terms: D000179:Acrylates / Q000737:chemistry*; D000284:Administration, Oral; D000818:Animals; D002121:Calcium Channel Blockers / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D002626:Chemistry, Pharmaceutical; D004435:Eating; D005215:Fasting; D018565:Food-Drug Interactions; D066298:In Vitro Techniques; D008297:Male; D011108:Polymers / Q000737:chemistry*; D051381:Rats; D017208:Rats, Wistar; D000068296:Risedronic Acid / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D013270:Stomach / Q000187:drug effects*
chemical_list: D000179:Acrylates; D002121:Calcium Channel Blockers; C477020:Eudragit E100; D011108:Polymers; D000068296:Risedronic Acid
keywords: Bioavailability enhancement; Complex; Eudragit E; Food interaction; Gastric damage; Risedronate