Degradation Kinetics of Water-Insoluble Lauroyl-lndapamide 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.