Risedronate pharmacokinetic studies after oral administration to rats of loaded TiO2 nanoparticles

Risedronate is indicated for the treatment and prevention of osteoporosis. The oral route is the most preferred for chronic drug therapy, even if it induces some disadvantages such as poor absorption (less than 1% of the dose) and dangerous adverse gastrointestinal effects. We propose a new formulation consisting in a colloidal suspension obtained by risedronate adsorption (up to 7%) on a slurry of colloidal TiO2 nanoparticles. The particles were prepared by hydrolysis of titanium isopropoxide. The drug adsorbed appeared no more water soluble in the pH range 0-5 and it was desorbed from TiO2 nanoparticles in the pH range 6-14, where it became water soluble. This behaviour should allow for protecting the gastric mucosa after oral administration. We have performed a comparison of the risedronate pharmacokinetic profile after its oral administration to rats as water solution or as TiO2 colloidal suspension form. After the water solution administration (60 mg of drug), risedronate was detected in the bloodstream with at tmax of about 30 min and became undetectable after 4 hours. On the other hand, the administration of the colloidal suspension allowed us to obtain a controlled release of the drug in the bloodstream up to 8 hours and a relative bioavailability up to 185%, calculated as ratio of AUC values obtained for the adsorbed and free drug. This behaviour could imply an improvement of the risedronate therapeutic effects and a reduction of its frequency of administration with a consequent amelioration of the beneficial/risk ratio.