SOLUBILITY ENHANCEMENT OF CANDESARTAN CILEXETIL BY USING DIFFERENT HYDROTROPIC AGENTS

Jaya Singh*, Dr.S.K.Umadevi, Sai vardhan, Manisha Lachoriya, G.Rajeswari, B.Kasturibai.

ABSTRACT

Conventional Candesartan Cilexetil is practically insoluble in water, have slow onset of action and poor bioavailability (15-20%), and therefore cannot be given in emergency clinical situations like hypertension or pulmonary edema. The purpose of research is to provide a fast dissolving oral dosage form of candesartan, which can provide quick onset of action by using the concept of mixed hydrotropy. Initially solubility of candesartan is determined individually in 4 hydrotropic agents namely urea, sodium acetate, sodium benzoate and sodium citrate at concentration of 10, 20, 30 and 40% w/v solutions using purified water as solvent. Highest solubility was obtained in 40% sodium benzoate solution. Different combinations of all hydrotropic agents in different ratios were used to determine solubility, so that total concentration of hydrotropic agents was always 40%. Highest solubility was obtained in solution which contains (sodium acetate,sodium benzoate,sodium citrate )at optimum ratio of 13.33. This optimized combination was utilized in preparing solid dispersions by common solvent evaporation technique using distilled water as solvent. Solid dispersions were evaluated for flow properties like bulk density, tapped density, angle of repose, compressibility index, hausner ratio and SEM. Dissolution studies of solid dispersion were done using USP Type II apparatus. It was concluded that the concept of mixed hydrotropic solid dispersion is novel, safe and cost-effective technique for enhancing the bioavailability of poorly water-soluble drugs by dissolving drug in non ionized form. The magical enhancement in solubility of Candesartan Cilexetil is clear indication of its potential to be used in future for other poorly water-soluble drugs in which low bioavailability is major concern.

Keywords: Bioavailability, Candesartan Cilexetil, Mixed Hydrotropy, Solid Dispersion.