Degradation kinetics of water-insoluble lauroyl-indapamide in aqueous solutions: prediction of the stabilities of the drug in liposomes.
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.
Suo
Xu Bin
XB
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
Deng
Ying Jie
YJ
Zhang
Han
H
Wang
Yu Qiang
YQ
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
D000959:Antihypertensive Agents; D002021:Buffers; D008081:Liposomes; D012996:Solutions; D012997:Solvents; C502363:lauroyl indapamide; D014867:Water; D000096:Acetone; D007190:Indapamide