NanoActive Telmisartan

Bioavailability of orally administered Telmisartan is limited by its very low aqueous solubility. Unformulated, only a small fraction of the drug reaches the systemic circulation. In vitro solubility tests showed that nanoformulation of Telmisartan resulted in significant improvement both with respect to apparent solubility (figure 1) and dissolution rate. USP dissolution testing of NanoActive Telmisartan in a tablet formulation also showed improved dissolution properties when compared to the dissolution properties of tablets with the same composition containing the reference compound and similar dissolution characteristics with higher overall drug release when compared to the commercial benchmark (figure 2).

Solubility enhancement of Telmisartan
by the proprietary NanoActive™ technology
Figure1

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

PAMPA permeability. Concentration of Telmisartan in the receiver compartment (C_R)
after different incubation times for reference and NanoActive Telmisartan
Figure3

PAMPA permeability measurements under sink conditions demonstrated a significant increase in apparent permeability of the sample containing NanoActive Telmisartan 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 Telmisartan. Exposure (AUC) and maximal plasma concentration (c_max) showed several fold increase in rat studies under fasted and fed conditions (figures 4 and 5).

Serum concentrations of Telmisartan after oral administration
of 30 mg/kg NanoActive and reference test
substance in rats under fasted condition
Figure4

Serum concentrations of Telmisartan after oral administration
of 30 mg/kg NanoActive and reference test
substance in rats under fed condition
Figure5