NanoActive Candesartan Cilexetil

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).

Solubility enhancement of Candesartan Cilexetil by
the NanoActive™ technology platform
Figure1

USP dissolution test of tablets containing reference Candesartan Cilexetil,
NanoActive and of the commercially available tablet
Figure2

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 (c_max) showed several fold increase in rat studies under fasted conditions (figure 4).

Concentration of Candesartan Cilexetil in the
receiver compartment (C_R) after different incubation times
for the reference and the NanoActive formulation
Figure3

Serum concentrations of Candesartan Cilexetil after oral
administration of 10 mg/kg NanoActive Candesartan Cilexetil
and reference test substance in rats under fasted condition
Figure4