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 (TiO2) particles have been developed and characterized in order to improve the bioavailability of orally administrated bisphosphonates. Nanocrystalline and colloidal TiO2, 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 50 nm and 90 nm grouped in clusters of about 0.2 μm and 2.5 μm, 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 8 h 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.