Effect of Citric Acid and Tromethamine on the Stability of Eyedrops Containing Lifitegrast

Abstract

Background/Objectives: Lifitegrast is an effective treatment for dry eye disease, reducing inflammation and improving the ocular surface condition. Owing to its high sensitivity to oxidation and hydrolysis, formulation studies are required to maintain the physicochemical stability of lifitegrast. This study aimed to overcome the instability of lifitegrast by developing a more stable eyedrop formulation by using citric acid and tromethamine to prevent the degradation of lifitegrast. Methods: Based on the Design of Experiment (DoE) approach, formulations were prepared at various concentrations of two stabilizers, citric acid and tromethamine. The stabilizers were carefully controlled to reduce the generation of degradation products. The eyedrops were stored under accelerated test conditions, and parameters such as appearance, pH, drug content, and impurities were evaluated. Results: The results showed that all critical quality attributes (CQAs) including appearance, pH, drug content, and impurities were maintained at stable levels under accelerated conditions, meeting established criteria. In addition, it was suggested that citric acid provided protection against oxidative stress, while tromethamine prevented hydrolysis caused by pH fluctuations. Conclusions: Consequently, it was concluded that the developed lifitegrast-containing eyedrop formulation exhibited improved physicochemical stability, validated through statistical analyses. These findings contribute to the development of stable eyedrops and provide a foundation for commercial production and clinical applications.