title: Degradation kinetics of water-insoluble lauroyl-indapamide in aqueous solutions: prediction of the stabilities of the drug in liposomes.
abstract: The aim of this study was to explore the degradation kinetics of water-insoluble lauroyl-indapamide in solutions and predict the stabilities of lauroyl-indapamide encapsulated in liposomes. Buffer-acetone (9:1) was used as the reaction solution and the reaction temperature was maintained at 60 degrees C. The correlation of the apparent degradation constants (k(obs)) of lauroyl-indapamide in liposomes and in buffer-acetone solutions at different pH has been explored. The degradation of lauroyl-indapamide in solutions was found to follow pseudo-first-order kinetics and was significantly dependent on the pH values. Lauroyl-indapamide was the most stable at pH 6.8, increasing or decreasing the pH of the solutions would decrease its stabilities. Buffer concentration had some effects on the stabilities of lauroyl-indapamide. The degradation active energies Ea were 68.19 kJ x mol(-1), 131.75 kJ x mol(-1) and 107.72 kJ x mol(-1) at pH3.6, 6.8 and 12 respectively in acetone-free buffer solutions (0.05M) calculated according to the Arrhenius equation with the extrapolation method. The apparent degradation constants (kobs) of lauroyl-indapamide in liposome and in buffer-acetone (9:1) solutions showed a good correlation at different pH levels, which indicates that the stabilities of the drug that dissolved in acetone-buffer mixture solutions can be used to predict the stabilities of the drug in liposomes as well.
authors: Institute of New Drug Research, School of Pharmacy, Jinan University, P.O.Box9, No.601 Huangpu Road West, Guangzhou 510632, P.R. China. suoxubin04@hotmail.com
authors: Xu Bin
authors: XB
authors: Suo
authors: Ying Jie
authors: YJ
authors: Deng
authors: Han
authors: H
authors: Zhang
authors: Yu Qiang
authors: YQ
authors: Wang
mesh_terms: D000096:Acetone / Q000737:chemistry; D000959:Antihypertensive Agents / Q000737:chemistry*; D002021:Buffers; D002851:Chromatography, High Pressure Liquid; D004355:Drug Stability; D006863:Hydrogen-Ion Concentration; D007190:Indapamide / Q000031:analogs & derivatives* / Q000737:chemistry; D007700:Kinetics; D008081:Liposomes; D015394:Molecular Structure; D009994:Osmolar Concentration; D012995:Solubility; D012996:Solutions; D012997:Solvents / Q000737:chemistry; D013696:Temperature; D013997:Time Factors; D014867:Water / Q000737:chemistry
chemical_list: D000959:Antihypertensive Agents; D002021:Buffers; D008081:Liposomes; D012996:Solutions; D012997:Solvents; C502363:lauroyl indapamide; D014867:Water; D000096:Acetone; D007190:Indapamide