Research Article The Effect of Polysorbate 20 on Solubility and Stability of Candesartan Cilexetil in Dissolution Media

Abstract. The addition of polysorbate 20 (T20) is required to achieve “sink ” conditions during a dissolu-tion test for tablets with candesartan cilexetil (CC). Polysorbate 20 (0.35%–0.7%w/w) added to 0.05 mol/L of phosphate buffer pH 6.5 dramatically increased the apparent solubility of the drug from 0.8 μg/ml even to 353 μg/ml, while its effect in lower pH or in water was much smaller (20 μg/ml in pH 4.5). The increased concentration of phosphate salts (0.2 mol/l) at pH 6.5 in the presence of 0.7 % of polysorbate 20, resulted in further increase of candesartan cilexetil solubility to 620 μg/ml. The change of pH from 1.2 to 7.4 resulted in a 1.5-fold increase of the activation energy and, depending on temperature, 8–14-fold decrease of the degra-dation rate. When polysorbate 20 increased the activation energy 2-fold, independent of pH, it protected candesartan cilexetil from degradation; however, this effect was temperature dependent andwas very small at 310 K—the degradation rate in pH 6.5 decreased by 13 % only. It was calculated that in the phosphate buffer pH 6.5 with polysorbate, one can expect during 24 h the degradation at the level of 9.3%, thus a flow-through dissolution apparatus was recommended for testing prolonged release dosage forms. KEY WORDS: candesartan; dissolution; polysorbate; solubility; stability