Stability of vancomycin 50 mg/mL eye drops in low density polyethylene (LDPE) multidose eyedropper
The objective of this study was to assess the physicochemical stability of vancomycin eye drops at 50 mg/mL in LDPE multidose eyedroppers stored in three different ways: in the freezer (-20°C), in the refrigerator (2-8°C) and at room temperature (20-25°C).
The pilot batch consisted of 90 multidose eyedroppers of 8 mL prepared in an isolator by reconstituting vancomycin powder for solution for injection 1g (Mylan®) in sterile water for injection. The physicochemical stability was evaluated by assaying the active component as well as monitoring impurities and degradation products by High Performance Liquid Chromatography coupled with UV-visible spectrophotometry, measurement of pH, osmolarity and visual inspection of the preparation. These parameters were measured at six stages of the study: the day of manufacture (D0), 7 days, 14 days, 1 month, 2 months and 3 months after manufacture (D7, D14, M1, M2, M3).
The vancomycin concentration of eye drops stored in the freezer and in the refrigerator remained stable during the study. At 3 months, the vancomycin concentration was 98.9% ± 2.8% of the concentration on D0 for eye drops stored at -20°C and 98.8% ± 1.8% for eye drops stored between +2 and +8°C. At room temperature, the percentage of degradation of vancomycin was less than 10% up to M1 with a concentration at 92.0% ± 0.7% of the value at D0, this decreased at M2 going to 88.1% ± 0.5%. The decrease in the concentration of vancomycin is correlated with the increase in the concentration of its degradation products described in the monograph of the European Pharmacopoeia. The pH remained stable for eye drops stored in the freezer and in the refrigerator, varying between 3.23 ± 0.06 and 3.37 ± 0.03 during the study. A pH excursion was observed for eye drops stored at room temperature (3.26 on D0 and 3.63 on M2). Similarly, osmolarity remained stable for eye drops stored in the freezer and in the refrigerator (between 38 and 39 mOsm/L) while it increased from 39 to 42.3 mOsm/L at room temperature. All solutions remained clear and colorless during the study.
The physicochemical stability of vancomycin at 50 mg/mL in LDPE eyedroppers has been demonstrated at 3 months when stored at -20°C and between +2 and +8°C. At room temperature, eye drops are only stable for 1 month. In hospital or outpatient practice, storage in the refrigerator seems the most suitable, and room temperature data can be useful in the event of temperature fluctuations during storage of the eyedroppers. This work should be supplemented by a microbiological stability study also including the opening of the containers, simulating the real conditions of use.