Stability study of topotecan in ophthalmic prefilled syringes for intravitreal delivery - Original research

Q: Why is stability data important for using TPT in prefilled syringes?

TPT has limited stability data, and its use in prefilled syringes requires evidence that the drug remains stable under realistic storage conditions to support safe preparation and administration.

Q: How was TPT stability evaluated in the study?

Stability was assessed using reversed-phase liquid chromatography coupled with a diode array detector, including visual inspection and pH measurement over 12 months.

Q: What storage conditions showed the best stability results for TPT?

TPT solutions at 20 µg/mL and 200 µg/mL were stable at 5±3°C and −20±5°C for up to 12 months, with no precipitate and no significant changes in pH and concentration.

Sep 29, 2026

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Intravitreal and intracameral administration of melphalan and topotecan (TPT) has demonstrated efficacy in retinoblastoma treatment. Owing to rapid hydrolysis, melphalan must be used within an hour after reconstitution, while improved room-temperature stability and reduced ocular toxicity make TPT a promising option for prefilled syringes. Due to limited TPT stability data, TPT stability was assessed at 20 µg/mL and 200 µg/mL under three storage conditions.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages6

Reading Time15 min

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Abstract

Background

Introduction

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Original research Stability study of topotecan in ophthalmic prefilled syringes for intravitreal delivery William Bello , 1,2,3 Camille Hosotte , 1,2,3 Camille Stampfli , 1 Antoine Pierrot, 1 Francis L Munier,4 Markoulina Berger-Gryllaki,1 Julian Pezzatti , 1 Laurent Carrez , 1 Farshid Sadeghipour 1,2,3 ► Additional supplemental material is published online only. To view, please visit the journal online ([https://](https://)[ ](https://)[doi.org/10.1136/ejhpharm-](doi.org/10.1136/ejhpharm-)[ ](doi.org/10.1136/ejhpharm-)[2024-004346](2024-004346)) . 1Pharmacy Department, Lausanne University Hospital, Lausanne, Switzerland 2School of Pharmaceutical Sciences, University of Geneva, Geneva, Switzerland 3Center for Research and Innovation in Clinical Pharmaceutical Sciences, Lausanne University Hospital and Univerity of Lausanne, Lausanne, Switzerland 4Jules-Gonin Ophthalmic Hospital, Lausanne, Switzerland Correspondence to Professor Farshid Sadeghipour; farshid.sadeghipour@chuv.ch Received 5 September 2024 Accepted 23 December 2024 EAHP Statement 3: Production and Compounding. © European Association of Hospital Pharmacists 2025. Re-use permitted under CC BY-NC. No commercial re-use. Published by BMJ Group. To cite: Bello W, Hosotte C, Stampfli C, et al. Eur J Hosp Pharm Epub ahead of print: [please include Day Month Year] . doi:10.1136/ ejhpharm-2024-004346 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 bea promising candidate for production of prefilled syringesin 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 syringesin 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. INTRODUCTION Retinoblastoma, described as the most prevalent paediatric intraocular cancer, is lethal by metastasis if left untreated.1–3 The primary goal of retinoblastoma treatment is to prevent metastatic disease and preserve life. Eye conservative treatment using chemotherapy aims to prevent enucleation and preserve vision in the affected eye with minimal side effects to the patient and impact on their quality of life.2 4 Intravitreal and intracameral injections allow for direct exposure of the avascular vitreous and aqueous humours to high concentrations of chemotherapy by bypassing the blood–retinal barrier. This also results in low plasma exposure thus minimising systemic side effects.5 6 Intravitreal melphalan therapy emerged in 2012 as a promising administration technique for active recurrent or persistent vitreous seeds.7 8 In 2017, WHAT IS ALREADY KNOWN ON THIS TOPIC | ⇒ Intravitreal and intracameral administration of melphalan and topotecan (TPT) has shown efficacy in the treatment of re

FAQs

Why is stability data important for using TPT in prefilled syringes?

TPT has limited stability data, and its use in prefilled syringes requires evidence that the drug remains stable under realistic storage conditions to support safe preparation and administration.

How was TPT stability evaluated in the study?

Stability was assessed using reversed-phase liquid chromatography coupled with a diode array detector, including visual inspection and pH measurement over 12 months.

What storage conditions showed the best stability results for TPT?

TPT solutions at 20 µg/mL and 200 µg/mL were stable at 5±3°C and −20±5°C for up to 12 months, with no precipitate and no significant changes in pH and concentration.

Sep 29, 2026

Upload by OmBimo