Degradation Kinetics of Water-Insoluble Lauroyl-Indapamide in Aqueous Solutions: Prediction of the Stabilities of the Drug in Liposomes

• Published in: Archives of pharmacal research Vol. 30; no. 7; pp. 876 - 883
• Main Authors: Deng, Ying-Jie, Zhang, Han, Wang, Qiang, Suo, Xu-Bin
• Format: Journal Article
• Language: Korean
• Published: 대한약학회 01.07.2007
• Subjects: 약학; Water-insoluble; Liposomes; Aqueous solutions; Degradation kinetics; Lauroyl-indapamide
• ISSN: 0253-6269; 1976-3786

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 $60^{\circ}C$. 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 $68.19\;kJ{\cdot}mol^{-1}$, $131.75\;kJ{\cdot}mol^{-1}$ and $107.72\;kJ{\cdot}mol^{-1}$ 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 ($k_{obs}$) 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.