Stability of frozen 1% voriconazole eye-drops in both glass and innovative containers

Abstract Purpose To assess the physico-chemical stability of Voriconazole Eye-Drops (VED), when stored frozen and refrigerated once thawed, in 3 containers: Amber glass with a Low-Density PolyEthylene (LDPE) eyedropper, and two types of LDPE bottles: one classical and one with an innovative insert that maintains sterility after opening (Novelia® from Nemera) Methods : Three batches of 1% VED (10 mL) were aseptically compounded from marketed injectable voriconazole (Vfend®) diluted in sterile water for injection. VEDs were stored for three months at -20°C in amber glass (n=32), classical LDPE (n=32) or innovative LDPE (n=31) bottles. Stability-indicating (HPLC-UV-DAD) and chiral chromatography methods were developed. The stability study was conducted according to GERPAC-SFPC guidelines. At each study time, the following parameters were controlled: visual aspect, voriconazole concentration, pH and osmolality. In addition, non-visible particle count, sterility and absence of racemisation (impurity D – (2S,3R)-voriconazole) were assessed at the beginning and end of the study. Results are expressed as mean ± standard deviation. Statistical analyses were performed using non-parametric tests (α Results When stored frozen, concentration was between 95.2±1.4% and 103.6±1.3% of the initial concentration (C0) with no difference between the three containers (p=0.564; non-significant). Fifteen days after thawing, concentration was between 97.1±1.6% and 98.6±0.8% of C0 with no difference between containers (p=0.278 and 0.368 for VED thawed at room temperature and at 2-8°C, respectively). pH remained stable between each time. Osmolality was slightly higher in glass (533.17 ± 8.93 mOsm/Kg) than in plastic containers (522.17±3.31mOsm/Kg, classical LDPE; 517.5±12.42 mOsm/Kg, innovative LDPE) (p=0.022). Sterility was preserved. Degradation product areas increased slightly but remained below the limit of quantification. Impurity D was never detected. Conclusion We have demonstrated that the ability of the innovative container Novelia® to maintain VED physicochemical and microbiological stability does not differ from that of amber glass and classical LDPE containers. Real life studies are required to find out if there is a potential difference between Novelia® and other containers in terms of sterility preservation.