PP-044 Stability of 50 and 100 µg/0.1 ml intraocular solutions of voriconazole at 2–8°c

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Abstract

Background

Voriconazole is a triazole antifungal agent effective in most cases of keratitis caused by fungi. Off-label use of extemporaneously compounded intraocular (intrastromal, intracameral) voriconazole has shown promising results in deep fungal ophthalmic infections, and abscessed, recurrent or drug resistant eye infections. Stability data on voriconazole intraocular solutions (VIS) are lacking.

Purpose

To assess the stability of 50 and 100 µg/0.1mL VIS stocked at 2–8°C.

Material and methods

2 batches of VIS (2 mL; 1 batch per concentration) were aseptically compounded from injectable Vfend (Pfizer) and Ringer’s lactate solution (Baxter), stored at 2–8°C in 3 part syringes (n=66) and analysed on day 13 (D13) and after 1 (D30) and 1.5 (D44) months. Stability study was led according to the GERPAC-SFPC stability studies guidelines. At each time point, visual aspect was checked, and voriconazole relative concentration (% of initial concentration, using a stability indicating HPLC-UV-diode-array-detector method), pH and osmolality were measured. Non-visible particle counts (using light obscuration particle count test) for particle size ≥ 10 µm and ≥25 µm (Eur Pharm 2.9.19 threshold: 6000 and 600/recipient, respectively) and sterility were assessed. Statistical analysis was carried out using non-parametric tests (α <5%). Degradation rates were compared with a Student t test.

Results

For every time point, CI relative concentrations were (0.993; +infinite (and) 0.951; +infinite (respectively, for 50 and 100 µg/0.1 mL), and remained superior to 95% (p<0.0001). No difference was shown in degradation rates (0.008±0.120 and −0.231±0.961 (p=0.497)) between the 2 concentrations, indicating no concentration effect. Osmolality remained stable (from 281.2 (T0) to 282.2 (D44) and from 298.2 to 299.8 mOsm/kg (p=0.490)). pH increased from 6.78 (T0) to 7.11 (D44) (p=0.150). Particles size ≥ 10 µm rose from 240.3 (D13) to 339.1 (D44) and from 363.2 to 487.6 particles/syringe, respectively, for 50 and 100 µg/0.1 mL. Particles size ≥ 25 µm rose on D13 from 3.3 to 4.4 and from 5.2 to 6.9 particles/syringe respectively. For voriconazole degradation products, whose toxicity is unknown, areas increased by a maximum of 1.3 (D13) and 2 (D44), remaining unquantifiable.

Results

Sterility was preserved to at least D13 with no change in visual aspect.

Conclusion

VIS remained stable for 13 days at 2–8°C. We advise a shelf-life of a maximum of 13 days for both VIS kept at 2–8°C.

Conclusion

No conflict of interest

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