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

GUZMAN ML; SORIA EA; LAÍNO C; MANZO RH; OLIVERA ME

EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS

ELSEVIER SCIENCE BV

Lugar: Amsterdam; Año: 2016 vol. 107 p. 263 - 272

0939-6411

Novel complexes 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 histologic analysis in an experimental rat model. The degree of counterionic condensation between Eudragit E100 and risedronate was assessed by dialysis. Mechanistic information about the interaction with calcium and the release of risedronate from the complexes was obtained using physiologic solution and simulated gastric fluid without pepsin. Non-significant differences were observed in the urinary excretion of risedronate when the complex or free risedronate were 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 they were concomitantly administered with food. Such behavior was related to the high degree of counterionic condensation in the complex (86.5%) which enabled a significant reduction of the rate and magnitude of risedronate precipitation in the presence of calcium. It also allowed a decrease in the gastroduodenal damage from the complex, evidenced by a lower frequency of gastric mucosae hemorrhage. A sustained release of risedronate from the complex was observed towards water, simulated gastric fluid or physiologic solution, through an ionic-exchange mechanism.