UNITEFA 23945
UNIDAD DE INVESTIGACION Y DESARROLLO EN TECNOLOGIA FARMACEUTICA
Unidad Ejecutora - UE
artículos
Título:
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
Autor/es:
LAINO CARLOS HORACIO; GUZMÁN ML; MANZO RH; SORIA, ELIO; OLIVERA MARIA EUGENIA
Revista:
EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS
Editorial:
ELSEVIER SCIENCE BV
Referencias:
Lugar: Amsterdam; Año: 2016 vol. 117 p. 263 - 272
ISSN:
0939-6411
Resumen:
Novel complexes consisting of Eudragit E100-risedronate are presented. The oral bioavailability of risedronatein rats was determined through its percentage excreted in urine after administration of complexedor free risedronate in fed and fasted conditions. The evaluation of the risedronate gastroduodenalirritation potential was carried out by macroscopic and histological analyses in an experimentalrat model. The degree of counterionic condensation between Eudragit E100 and risedronate was assessedby dialysis with, mechanistic information about the interaction with calcium and the release of risedronatefrom the complexes being obtained using physiological solution and simulated gastric fluid withoutpepsin. Non-significant differences were observed in the urinary excretion of risedronate when thecomplex or free risedronate was administered to fasted rats. However, the urinary excretion of risedronatein the complex group was 4-times higher than in the free risedronate group when animals wereconcomitantly administered with food. This behavior was related to the high degree of counterionic condensationin the complex (86.5%), which led to a reduction in the calcium induced rate and magnitude ofrisedronate precipitation and resulted in a decrease in the gastroduodenal damage from the complex, asevidenced by a lower frequency of gastric mucosae hemorrhage. A sustained release of risedronate fromthe complex was observed toward water, simulated gastric fluid or physiological solution, through anionic-exchange mechanism. In conclusion, complexation with Eudragit E100 could be a useful strategyto overcome the unfavorable properties of risedronate.
