Particulate adducts based on sodium risedronate and titanium dioxide for the bioavailability enhancement of oral administered bisphosphonates.
Adducts based on a bisphosphonate drug (sodium risedronate) and titanium dioxide (TiO(2)) particles have been developed and characterized in order to improve the bioavailability of orally administrated bisphosphonates. Nanocrystalline and colloidal TiO(2), both characterized by powder X-ray diffraction, were used to obtain the adducts 1 and 2, respectively. Adducts 1 and 2 appeared constituted by nanoparticles of about 50nm and 90nm grouped in clusters of about 0.2microm and 2.5microm, respectively. Higher amounts of drugs were adsorbed on adduct 2 (7.2+/-0.3%) with respect to adduct 1 (4.0+/-0.3%). In vitro studies demonstrate that the adducts were able to release the drug in the pH range of 6-9, whereas they remained essentially stable in the pH range of 0-5. In vivo studies indicate that after oral administration to male Wistar rats, the microparticles of adduct 2 were able to prolong the presence of risedronate in the bloodstream during an 8h period, resulting in a relative bioavailability almost doubled with respect to the free drug. This behaviour allows envisioning an improvement of the risedronate therapeutic effects and/or a reduction of its frequency of administration with consequent reduction of gastro-oesophageal injuries typically induced by oral administration of bisphosphonates.
Dissette
Valeria
V
Department of Chemistry, University of Ferrara, via Borsari 46, Ferrara, Italy.
Bozzi
Pietro
P
Bignozzi
Carlo Alberto
CA
Dalpiaz
Alessandro
A
Ferraro
Luca
L
Beggiato
Sarah
S
Leo
Eliana
E
Vighi
Eleonora
E
Pasti
Luisa
L
D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D002851:Chromatography, High Pressure Liquid; D004164:Diphosphonates / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics; D012968:Etidronic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry / Q000493:pharmacokinetics; D008297:Male; D008855:Microscopy, Electron, Scanning; D051381:Rats; D017208:Rats, Wistar; D000068296:Risedronic Acid; D014025:Titanium / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics; D014961:X-Ray Diffraction
D004164:Diphosphonates; C009495:titanium dioxide; D014025:Titanium; D000068296:Risedronic Acid; D012968:Etidronic Acid