Chemical stability and physical compatibility of frozen vancomycin oral solution

Oral vancomycin is a first-line treatment for Clostridioides difficile infection. When used as an oral solution, its beyond-use date is limited to 14 days in an opened container and at 2-8 °C, according to the guidelines set out in the Guide to Good Preparation Practices for Medicines in Hospital Pharmacy Services. This complicates batch preparation in order to meet the increasing demand for this medication. This study evaluated the physicochemical stability of vancomycin hydrochloride in oral solution under freezing and subsequent thawing conditions.

An oral solution of vancomycin hydrochloride was prepared at a concentration of 12.5 mg/mL, and aliquots were packaged in two types of containers (transparent polypropylene cup and amber polyethylene terephthalate bottle). The aliquots were frozen at -25 °C. After 1, 7, 14, 21, 35, 60, 88, and 123 days, they were thawed and then stored at 2-8 °C for 14 days. Residual concentration was determined using an Agilent Technologies 1100 HPLC system (at t = 0, 3, 6, 10, and 14 days after thawing), and physical compatibility was assessed by pH measurement using a pH meter (model 3510, Jenway, UK) with a glass electrode, as well as by visual inspection.

The residual concentration of vancomycin hydrochloride remained ≥91.9% of its initial concentration (12.5 mg/mL) for up to 123 days under frozen storage (-25 °C) and after 14 days under refrigeration (2-8 °C). The pH variation was ≤ ± 0,18, and no changes in color, turbidity, or precipitate formation were detected in any of the aliquots.

Vancomycin hydrochloride oral solution at a concentration of 12.5 mg/mL maintains its physicochemical stability for up to 123 days under frozen storage and after thawing followed by storage for 14 days at 2-8 °C, regardless of photoprotection.