Abstract
Telmisartan, an orally active nonpeptide angiotensin II receptor antagonist is a BCS
Class II drug having aqueous solubility of 9.9 µg/ml and hence oral bioavailability
of 40%. The present study involved preparation of nanosuspensions by evaporative antisolvent
precipitation technique to improve the saturation solubility and dissolution rate
of telmisartan. Various stabilizers such as TPGS, PVPK 30, PEG 6000 were investigated
of which TPGS was found to provide maximum decrease in particle size and accord greater
stability to the nanosuspensions. Box-Behnken design was used to investigate the effect
of independent variables like stabilizer concentration, time and speed of stirring
on particle size of nanosuspensions. Pharmacodynamic studies using Goldblatt technique
were undertaken to evaluate the effect of nano-sizing on the hypotensive effect of
the drug. Concentration of TPGS and speed of rotation were found to play an important
role in particle size of the nanosuspensions whereas time of stirring displayed an
exponential relationship with particle size. Freeze dried nanocrystals obtained from
nanosuspension of least particle size were found to have increased saturation solubility
of telmisartan in different dissolution media. The reconstituted nanosuspension was
found to reduce both systolic and diastolic blood pressure without affecting pulse
pressure and heart rate. Statistical tools can be used to identify key process and
formulation parameters which play a significant role in controlling the particle size
in nanosuspensions.
Key words
telmisartan - nanosuspensions - Box-Behnken design - Goldblatt technique
