title: Preformulation study of methazolamide for topical ophthalmic delivery: physicochemical properties and degradation kinetics in aqueous solutions.
abstract: 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.
authors.affiliation: School of Pharmacy, Nanjing Medical University, Hanzhong Road No. 140, Nanjing 210029, China.
authors.forename: Sunmin
authors.initials: S
authors.lastname: Jiang
authors.forename: Fengzhen
authors.initials: F
authors.lastname: Wang
authors.forename: Shuning
authors.initials: S
authors.lastname: Zhu
authors.forename: Xiumei
authors.initials: X
authors.lastname: Zhang
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Guo
authors.forename: Rui
authors.initials: R
authors.lastname: Li
authors.forename: Qunwei
authors.initials: Q
authors.lastname: Xu
mesh_terms: D060433:Administration, Ophthalmic; D002257:Carbonic Anhydrase Inhibitors / Q000008:administration & dosage* / Q000737:chemistry; D002626:Chemistry, Pharmaceutical; D004339:Drug Compounding; D016503:Drug Delivery Systems; D004355:Drug Stability; D004356:Drug Storage; D006863:Hydrogen-Ion Concentration; D006868:Hydrolysis; D007700:Kinetics; D008704:Methazolamide / Q000008:administration & dosage* / Q000737:chemistry; D009883:Ophthalmic Solutions; D009994:Osmolar Concentration; D012995:Solubility
chemical_list: D002257:Carbonic Anhydrase Inhibitors; D009883:Ophthalmic Solutions; D008704:Methazolamide