Stability of 10 mg/mL cefuroxime solution for intracameral injection in commonly used polypropylene syringes and new ready-to-use cyclic olefin copolymer sterile vials using the LC-UV stability-indicating method

• Published in: Drug development and industrial pharmacy 2016-01, Vol.42 (1), p.166-174
• Main Authors: Feutry, Frédéric, Simon, Nicolas, Genay, Stéphanie, Lannoy, Damien, Barthélémy, Christine, Décaudin, Bertrand, Labalette, Pierre, Odou, Pascal
• Format: Article
• Language: English
• Subjects: Anti-Bacterial Agents - administration & dosage; Anti-Bacterial Agents - chemistry; Anti-Bacterial Agents - therapeutic use; Antibiotic; aseptic filling process; Cefuroxime - administration & dosage; Cefuroxime - chemistry; Cefuroxime - therapeutic use; container-content interaction; Cycloparaffins - chemistry; Drug Compounding - standards; Drug Packaging - methods; Drug Stability; Drug Storage; endophthalmitis; Endophthalmitis - prevention & control; Feasibility Studies; Glass; injectable drug; Injections, Intraocular; Osmolar Concentration; Pharmaceutical Solutions - administration & dosage; Pharmaceutical Solutions - chemistry; Pharmaceutical Solutions - therapeutic use; plastic container; Polypropylenes - chemistry; Postoperative Complications - prevention & control; stability study; Syringes; Temperature
• ISSN: 0363-9045; 1520-5762
• DOI: 10.3109/03639045.2015.1038273

Context: Injecting intracameral cefuroxime has been found beneficial in reducing the risk of postoperative endophthalmitis but its use has been limited through a lack of approved marketing and of ready-to-use single-units as well as the problem of aseptic compounding. Objective: Our aim was to assess a new automated primary packaging system which should ensure a higher level of sterility, thanks to its closed, sterile, ready-to-use polymer vial called "Crystal® vial". The chemical stability of a 10 mg/mL cefuroxime solution was compared in 1 mL Crystal® vials and 1 mL Luer-lock polypropylene syringes (actual reference) to eliminate any potential and specific interactions with its cyclic olefin copolymer (COC) body and elastomer stopper. Methods: Cefuroxime solution was introduced into vials and syringes and stored at −20 °C, +5 °C and +25°C/60% Relative Humidity. Cefuroxime concentration and the relative amount of the main degradation product (descarbamoyl-cefuroxime) were both determined by an HPLC/UV method indicating stability. Solutions were considered steady if the concentration remained at over 90% of the initial value. In the adapted storage conditions, the evolution of osmolality, pH and sterility was assessed. Results: Stability profiles were identical between vials and syringes in all storage and temperature conditions. The solution was stable (cefuroxime concentration, pH and osmolality) and still sterile for 365 days at −20°C. The concentration fell below 90% after 21 days at +5 °C and after 16 h at +25°C/60%s relative humidity. Conclusions: The COC and thermoplastic elastomer of the vials had no impact on the degradation process confirming its possible use for a ready-to-use cefuroxime solution single-unit dose.