Cyclosporine a-loaded UniORV®: Pharmacokinetic and safety characterization

This study aimed to improve pharmacokinetic behavior and reduce safety concern of cyclosporine A (CsA) by UniORV® approach, a new platform for solid dispersion formulation. CsA-loaded UniORV® (UO/CsA) was prepared, and its physicochemical properties were evaluated in terms of droplet size distribution and dissolution. The pharmacokinetic behavior and nephrotoxic potential of orally-dosed CsA samples (10 mg-CsA/kg) were assessed in rats. After re-dispersion of UO/CsA in water, fine droplets were observed, and the mean diameter of droplets was calculated to be 45 nm. The UniORV® approach markedly improved the dissolution behavior compared with amorphous CsA in water. After oral administration of amorphous CsA, Neoral®, and UO/CsA in rats, UO/CsA exhibited a 32% lower maximum concentration and 5.1 h longer mean residence time than those of Neoral®. The oral absorption of CsA formulations was higher compared with amorphous CsA; in particular, the oral bioavailability of UO/CsA was 71-fold higher than that of amorphous CsA. Neoral® elicited nephrotoxicity with plasma creatinine level of 1.29 mg/dL; however, Neoral®-induced nephrotoxicity was attenuated in UO/CsA, as evidenced by a 15% lower plasma creatinine level of UO/CsA than that of Neoral®. From these findings, UO/CsA might be a promising dosage form with improved biopharmaceutical properties of CsA.