Evaluation of physicochemical stability of methimazole in topical formulation

Abstract

Introduction:Melasma is a skin hyperpigmentation disorder that occurs in sun-exposed areas such as face, the first line of treatment is hydroquinone; Due to recent concerns regarding the carcinogenicity of hydroquinone in long-term use, scientists are looking for a better alternative with fewer side effects. Clinical studies on topical use of methimazole have shown that this drug can prevent melanogenesis by inhibiting peroxidase and tyrosinase enzymes.Objective: The aim of our study is to reach the optimal formulation of the topical form of methimazole and to check the stability of this formulation in different storage conditions.Materials and methods: Methimazole was prepared in two bases, cold cream and vanishing cream, and stored under 3 different temperature and humidity conditions, refrigerator temperature, room temperature, and 40 ℃for 5 months, and the remaining percentage of the drug in different time periods was determined by a validated HPLC method. In all storage conditions, the kinetic of drug reduction were fitted to zero, first, second and third order models using Excel software. The shelf life in different storage conditions was calculated based on the time required for 10% degradation of the active substance. The significance of the data was checked and reported with statistical tests and GraphPad Prism software. Physical changes such as color change were also recorded and by digital images. Results:The results of HPLC show that the residual percentage of methimazole in both cream bases has decreased significantly after 5 months, and this decrease was more at 40℃ than at other temperatures. Kinetic of drug degradation follows F1 model. By comparing shelf lives vanishing cream is more stable than cold cream. Conclusion: The topical and semi-solid form of Methimazole in Vanishing Cream base is more stable than Cold Cream.