Physico-chemical stability of ceftazidime fortified eye drops 20 mg/mL stored at -20°C

Introduction
Infectious keratitis is one of the ophthalmic emergencies requiring the use of fortified ophthalmic solutions, including ceftazidime. Literature data indicate that ceftazidime solution is stable for several days at a temperature of 4-8°C. In order to avoid the destruction of unused product due to a short shelf life, the answer would be to freeze this eye drop.
The aim of this study was to investigate the physico-chemical stability of ceftazidime diluted with 0.9% NaCl to a concentration of 20 mg/mL, stored for 32 days at -20°C (then evaluated after thawing (4-8°C) for a period of 10 days) in an opaque polyethylene dropper bottle.

Materials and methods
Three batches of fortified eye drops have been prepared. At each time of analysis, 3 samples for each preparation was analysed by High Performance Liquid Chromatography coupled to a photodiode array detector at 260 nm. The stability indicating method was validated according to the ICH Q2 (R1). Physical stability was evaluated by visual and subvisual inspection (particle counting) as recommended by the European Consensus Conference. pH and osmolarity values were measured.

Results
Linearity was validated with an R² of 0.9999. Coefficients of variation for repeatability and intermediate precision were below 2%. Retention time was 4.3 min for ceftazidime. A total of 2 degradation products were characterized during the stability study. After 32 days of freezing, the initial concentration of ceftazidime was preserved at over 98.5%. After 5 days of thawing, the concentration remained above 95% of the initial concentration, rising to 92% after 10 days. For physical stability, no visual changes were detected, and subvisual counting for particles larger than 10 and 25 µm complies with the European Pharmacopoeia. Osmolality varied by less than 1.3% during the study. The maximum pH variation observed during the study was 0.22 units (from 7.17 to 6.95).

Conclusion
The physico-chemical stability of ceftazidime at a concentration of 20 mg/mL diluted in 0.9% NaCl and stored at -20°C in a polyethylene dropper bottle has been demonstrated for 32 days. Post-thaw stability was validated for 10 days.

See the poster