{
  "abstract": "Background and Importance The development of corneal haze is associated with pathological wound healing after photorefractive keratectomy, eye injury, and eye infections. Recently, losartan potassium 0.8 mg/mL eye drops administered six times daily (one drop per dose) over a period of 6 months were reported to be effective in treating corneal haze. As there is no authorised medicinal product available, losartan potassium 0.8 mg/mL eye drops must be provided as hospital pharmacy preparation.Aim and Objectives Formulation, preparation, and stability testing of preservative-free losartan potassium 0.8 mg/mL eye drops in Novelia multidose eye drop containers.Material and Methods For the preparation of a qualification batch, 130 mg losartan potassium (GMP compliant API) were exactly weighted and dissolved in 163 g of sterile 0.9% sodium chloride infusion solution under cleanroom conditions. 50 mL portions of the solution were drawn up into a 50 mL sterile plastic syringe, a 0.22 µm Minisart PES membrane filter connected and 10 mL portions of the solution filtered into sterile Novelia multidose eye drop containers (nominal volume 10 mL) each, sealed, and labelled. The content of one eye drop container was distributed into aerobic (8 mL) and anaerobic (2 mL) blood culture bottles for rapid sterility testing. 12 eye drop containers were stored at 2-8 °C and samples withdrawn at day 0, 14, 28, and 90 from three systems each. Physicochemical stability was determined in triplicate by quantitative HPLC analysis of intact losartan and by measuring pH and osmolality in parallel.Results At day 28, the losartan concentration amounted to 99.3% ± 0.9% RSD of the initially measured concentration. pH 6.2 and osmolality 288 mOsmol/kg fulfilled the pharmacopoeia specification of eye drops and remained nearly unchanged over 28 days. Refrigerated storage was chosen because of microbiological reasons and unknown stability at room temperature. The phosphate buffer-free formulation mitigates the risk of corneal calcification.Conclusion and Relevance The preparation of preservative-free losartan potassium 0.8 mg/mL eye drops was successfully implemented. The Novelia multidose eye drop container allows multiple administration of preservative-free solutions and efficient pharmacy preparation. Stability testing of the preparation is ongoing and shelf life proven for at least 1 month.Conflict of Interest No conflict of interest",
  "authors": [
    {
      "affiliations": [
        "University Medical Centre Johannes Gutenberg University Mainz, Pharmacy Department, Mainz, Germany"
      ],
      "name": "H Linxweiler"
    },
    {
      "affiliations": [
        "University Medical Centre Johannes Gutenberg University Mainz, Pharmacy Department, Mainz, Germany"
      ],
      "name": "J Reichhold"
    },
    {
      "affiliations": [
        "University Medical Centre Johannes Gutenberg University Mainz, Pharmacy Department, Mainz, Germany"
      ],
      "name": "I Krämer"
    }
  ],
  "title": "3PC-037 Formulation and stability of losartan 0.8 mg/ml eye drops for treatment of corneal haze",
  "uid": "5e66cc58-bcaa-5867-9c21-104a8be4266e"
}