Formulation Development of a pH-Adjusted, Preservative-Free 1% 5-Fluorouracil Eye Drop Compounded from Injectable...

Background: No licensed ophthalmic 5-fluorouracil (5-FU) product is available in Hungary, and published compounded 5-FU eye drops are alkaline dilutions of the injectable concentrate. We report a formulation development and 28-day storage-stability case study of a pH-adjusted, preservative-free 1% 5-FU eye drop prepared under Council of Europe Resolution CM/Res(2016)1. Methods: Five injectable concentrates were characterised for pH, and one was titrated with 0.1 N hydrochloric acid in a preservative-free ophthalmic vehicle to pH 7.30-7.60. Three 10 mL batches were prepared aseptically and release-tested; drop volume and delivered dose were determined on one batch, which was also followed for 28 days at 15-25 °C and 2-8 °C by inspection, pH, sterility and comparative HPLC-UV assay (single determinations). Results: All concentrates were alkaline (pH 8.95-9.18). The selected formulation reached pH 7.43; individual doses (mean 0.435 mg per drop) were within ±8% of the mean. At 15-25 °C, samples remained clear and sterile, with pH 7.41-7.51 and assay ≥ 97% of initial, without directional trend. At 2-8 °C, precipitate formed from day 7 and the supernatant assay fell to 89.1% by day 28. Conclusions: The preparation remained within specification for 28 days at controlled room temperature but not under refrigeration, consistent with, though not proven to result from, the lower solubility of un-ionised 5-FU. The 28-day period is provisional, not a validated shelf-life; in-use stability, osmolality and viscosity were not established.