Stability Study of 0.5 g/mL Urea Oral Solution in InOrpha®

Abstract

Abstract Background Urea is recommended in the 2nd line treatment in moderate to severe hyponatraemia induced by syndrome of inappropriate antidiuretic hormone secretion (SIADH), when water restriction is insufficient. A posology of 0.25–0.5 g/kg daily is suggested. A usual but inadequate urea oral preparation, i. e. 10 g urea powder dissolved in 100 mL water before use, was classically compounded. Therefore the pharmacy has developed a 0.5 g/mL urea oral liquid solution in InOrpha® with better organoleptic characteristics to improve treatment adherence and reduce the preparation time. The aim of this study was to determine physicochemical and microbiological stability of the urea oral liquid solution in order to establish a shelf life of the preparation. Methods The 0.5 g/mL urea solution was compounded using urea powder in a commercial suspending vehicle: Inorpha®. A validated high-performance liquid chromatographic (HPLC) method with UV detection was performed for the assay of urea. The preparations were packaged in amber glass bottles and stored at fridge (5 °C±3 °C) or at room temperature (24 °C±1 °C). The physicochemical (urea concentration, macroscopic change) and microbiological stability of the preparation was tested over 90 days. Urea concentration measurement at day 0 was considered as the reference value (100 % stability) and urea concentration in subsequent samples greater than 90 % were definite stable without macroscopic changes. Results The developed HPLC-UV method was validated in terms of linearity, specificity, accuracy and fidelity (less than 5 % for relative standard deviation and relative error). After 90 days, no microbial growth was noted and urea concentrations were always higher than 90 % of the initial concentration. Macroscopic changes were observed for the samples stored at fridge (5 °C+/− 3 °C) with massive crystallization of urea solution. Conclusions Although, all the preparations retain more than 95 % of the initial concentration after 90 days in all storage conditions, macroscopic change and pH change (more than 1 unit after 15 days at room temperature) have to be taken into account. The 0.5 g/mL urea oral liquid solution in InOrpha® remains stable for 15 days at room temperature (24 °C±1 °C) in amber glass bottles.