School of Pharmacy, Nanjing Medical University, Hanzhong Road No. 140, Nanjing 210029, China.
Int J Pharm. 2013 May 20;448(2):390-3. doi: 10.1016/j.ijpharm.2013.03.018. Epub 2013 Mar 29.
Methazolamide (MTZ) is an anti-glaucoma drug. The present paper aims to characterize the physicochemical properties and degradation kinetics of MTZ to provide a basis for topical ophthalmic delivery. With the increase in pH (pH 5.5-8.0) of aqueous solution, the solubility of the compound increased while the partition coefficient (Ko/w) which was estimated in the system n-octanol/aqueous solution decreased. The degradation of MTZ in aqueous solution followed pseudo-first-order kinetic. The degradation rate kpH is the rate in the absence of buffer catalysis. Plotting the natural logarithm of kpH versus the corresponding pH value gave a V-shaped pH-rate profile with a maximum stability at pH 5.0. The degradation rate constants as a function of the temperature obeyed the Arrhenius equation (R(2)=0.9995 at pH 7.0 and R(2)=0.9955 at pH 9.0, respectively). A decrease in ionic strength and buffer concentration displayed a stabilizing effect on MTZ. Buffer species also influenced the MTZ hydrolysis. Phosphate buffer system was more catalytic than tris and borate buffer systems. In brief, it is important to consider the physicochemical properties and the stability of MTZ during formulation.
甲醋唑胺（MTZ）是一种抗青光眼药物。本研究旨在表征 MTZ 的物理化学性质和降解动力学，为其局部眼用制剂提供依据。随着水溶液 pH 值（5.5-8.0）的增加，化合物的溶解度增加，而在正辛醇/水溶液体系中估算的分配系数（Ko/w）降低。MTZ 在水溶液中的降解遵循伪一级动力学。kpH 是无缓冲催化时的降解速率。以 kpH 的自然对数对相应的 pH 值作图，得到 V 形 pH-速率曲线，在 pH 5.0 时稳定性最高。降解速率常数随温度的变化符合阿伦尼乌斯方程（在 pH 7.0 时 R(2)=0.9995，在 pH 9.0 时 R(2)=0.9955）。离子强度和缓冲浓度的降低对 MTZ 具有稳定作用。缓冲种类也影响 MTZ 的水解。磷酸盐缓冲体系比三羟甲基氨基甲烷和硼酸盐缓冲体系具有更高的催化作用。总之，在制剂过程中考虑 MTZ 的物理化学性质和稳定性非常重要。
