Stability study of a 5 mg/mL oral vinorelbine solution in Inorpha^®

Introduction
Vinorelbine, used for maintenance treatment of pediatric rhabdomyosarcomas, is available as an injectable solution or soft capsule, forms that are not well-suited for outpatient care. Until now, our center produced an oral solution of vinorelbine diluted in 0.9% NaCl at 3 mg/ml. To improve the organoleptic properties and reduce administration volumes for our pediatric patients, we decided to replace the diluent with Inorpha^®.

Objective
The aim was to develop a 5 mg/ml oral preparation of vinorelbine in Inorpha^® and to evaluate its stability over time.

Materials and methods
Three batches of vinorelbine solution at a concentration of 5 mg/mL in Inorpha^® were prepared and stored at +4°C in amber glass bottles. Chemical stability was assessed using a previously validated stability-indicating HPLC-UV assay and by pH measurement. A variation of more than 1 pH unit was considered significant. Chemical stability was evaluated at T = 0 h, 24 h, 7 days, 15 days, 30 days, 2 months, and 6 months. According to GERPAC guidelines, the formulation was considered stable as long as the active ingredient content remained within 90–110% of the initial concentration and no degradation products were detected. Microbiological stability was evaluated at the conclusion of the study.

Results
The preparation was stable for 6 months. The mean pH for the three batches was initially 3.51 (± 0.01) compared to 3.97 (± 0.10) at the end of the study. The loss in content after 6 months was 6%, 4%, and 2% for each bottle, respectively, relative to the initial value. No degradation products were observed. All three batches of the preparation also remained sterile at 6 months.

Conclusion
This study demonstrates the feasibility and stability of a 5 mg/mL oral vinorelbine formulation in Inorpha^® (at pH 4) for 180 days when stored between +2°C and +8°C and protected from light. This formulation addresses the need for a new pediatric-friendly dosage form, improving the management of children undergoing maintenance treatment for rhabdomyosarcoma.

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