Bioavailability of orally administered Candesartan Cilexetil is limited by its very low aqueous solubility. In vitro solubility tests showed that formulation of Candesartan Cilexetil with the NanoActive™ technology resulted in significant improvement both with respect to apparent solubility (figure 1) and dissolution rate. USP dissolution testing of NanoActive Candesartan Cilexetil in a tablet formulation also showed improved dissolution properties when compared to the commercially available tablet, Atacand (figure 2).
We performed PAMPA permeability measurements under sink conditions and found that the apparent permeability of the sample containing NanoActive Candesartan Cilexetil is significantly higher when compared to the sample containing the reference compound (figure 3).
Improvement in apparent solubility and dissolution resulted in a substantial increase in oral bioavailability when compared to the unformulated reference Candesartan Cilexetil. Exposure (AUC) and maximal plasma concentration (cmax) showed several fold increase in rat studies under fasted conditions (figure 4).