Stability study of topotecan in ophthalmic prefilled syringes for intravitreal delivery.

Abstract

Background: Intravitreal and intracameral administration of melphalan and topotecan (TPT) has shown its efficacy in the treatment of retinoblastoma over the last few years. Due to rapid hydrolysis, melphalan must be administered within the hour following reconstitution. With improved stability at room temperature and reduced ocular toxicity, TPT seems to be a promising candidate for production of prefilled syringes in terms of safety and efficiency of preparation and treatment administration. Due to the lack of TPT stability data, the stability of TPT at 20 µg/mL and 200 µg/mL in prefilled syringes was evaluated in three different storage conditions.

Methods: The stability of TPT in prefilled syringes was assessed via reversed-phase liquid chromatography coupled to a diode array detector analytical platform. The physicochemical stability of TPT in prefilled syringes in both concentrations, stored at 30±2°C with a relative humidity (RH) of 65±5%, 5±3°C, and -20±5°C, was evaluated over 12 months including visual inspection and pH measurement.

Results: TPT solution in syringes at 20 µg/mL and 200 µg/mL was stable at 5±3°C and -20±5°C for up to 12 months, with no precipitate and no significant change in pH and concentration. A TPT-related degradant, 8-methoxy-TPT, was detected at <0.5% only in 30±2°C (65±5% RH) after 3 months.

Conclusion: This study demonstrated that TPT solutions at 20 µg/mL and 200 µg/mL conditioned in BBraun Omnifix syringes could be stored at 5±3°C for 12 months for safe and secure administration to patients.