Enhanced Antihypertensive Activity of Candesartan Cilexetil Nanosuspension: Formulation, Characterization and Pharmacodynamic Study
AbstractThe objective of the present investigation was to enhance the oral bioavailability of practically insoluble Candesartan cilexetil [CC] by preparing nanosuspension. The nanosuspension was prepared by media milling using zirconium oxide beads and converted to solid state by spray drying. The spray dried nanosuspension of CC [SDCN] was evaluated for particle size, zeta potential, saturation solubility, crystallanity, surface morphology and dissolution behavior. SDCN showed particle size of 223.5±5.4 nm and zeta potential of −32.2±0.6 mV while saturation solubility of bulk CC and SDCN were 125±6.9 μg/ml and 2805±29.5 μg/ml respectively, showing more than 20 times increase in solubility. Differential Scanning Calorimetry [DSC] and X-ray diffraction [XRD] analysis showed that crystalline state of CC remained unchanged in SDCN. Dissolution studies in phosphate buffer pH 6.5 containing 0.7% Tween 20 showed that 53±5% of bulk drug dissolved in 15 min whereas SDCN was almost completely dissolved exhibiting higher dissolution velocity and solubility. Transmission electron microscopy [TEM] revealed that nanocrystals were not of uniform size, and approximately of oval shape. Pharmacodynamic study based on deoxycorticosterone acetate [DOCA] salt model was performed in rats to evaluate in-vivo performance, which showed 26.75±0.33% decrease in systolic blood pressure for nanosuspension while plain drug suspension showed 16.0±0.38% reduction, indicating that increase in dissolution velocity and saturation solubility leads to enhancement of bioavailability of SDCN when compared to bulk CC suspension. Thus, the results conclusively demonstrated a significant enhancement in antihypertensive activity of candesartan when formulated as nanosuspension.
Scifeed alert for new publicationsNever miss any articles matching your research from any publisher
- Get alerts for new papers matching your research
- Find out the new papers from selected authors
- Updated daily for 49'000+ journals and 6000+ publishers
- Define your Scifeed now
DETROJA, C.; CHAVHAN, S.; SAWANT, K. Enhanced Antihypertensive Activity of Candesartan Cilexetil Nanosuspension: Formulation, Characterization and Pharmacodynamic Study. Sci. Pharm. 2011, 79, 635-652.
DETROJA C, CHAVHAN S, SAWANT K. Enhanced Antihypertensive Activity of Candesartan Cilexetil Nanosuspension: Formulation, Characterization and Pharmacodynamic Study. Scientia Pharmaceutica. 2011; 79(3):635-652.Chicago/Turabian Style
DETROJA, Chetan; CHAVHAN, Sandip; SAWANT, Krutika. 2011. "Enhanced Antihypertensive Activity of Candesartan Cilexetil Nanosuspension: Formulation, Characterization and Pharmacodynamic Study." Sci. Pharm. 79, no. 3: 635-652.