title: 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 dissolution 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 degradation 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 and was 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.
authors.affiliation: Department of Pharmaceutical Technology, Medical University of Gdansk, Hallera 107, Gdansk, 80-416, Poland.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Hoppe
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Sznitowska
mesh_terms: D047228:Angiotensin II Type 1 Receptor Blockers / Q000008:administration & dosage / Q000737:chemistry*; D001562:Benzimidazoles / Q000008:administration & dosage / Q000737:chemistry*; D001713:Biphenyl Compounds / Q000008:administration & dosage / Q000737:chemistry*; D002021:Buffers; D065546:Drug Liberation; D004355:Drug Stability; D005079:Excipients / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D000432:Methanol / Q000737:chemistry; D011136:Polysorbates / Q000737:chemistry*; D012995:Solubility; D012997:Solvents; D013501:Surface-Active Agents; D013696:Temperature; D013777:Tetrazoles / Q000008:administration & dosage / Q000737:chemistry*; D014867:Water / Q000737:chemistry
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D002021:Buffers; D005079:Excipients; D011136:Polysorbates; D012997:Solvents; D013501:Surface-Active Agents; D013777:Tetrazoles; D014867:Water; C077793:candesartan cilexetil; D000432:Methanol