3PC-039 Preparation and stability of ready-to-administer dexamethasone dihydrogen phosphate 8 mg/ml/0.02% hyaluronic acid intratympanal injection solution

<h3>Background and Importance</h3> Intratympanal injection of glucocorticoids is utilised to treat morbus menière which is characterised by vertigo, acute hearing loss, and tinnitus. As respective licensed products are not available, pharmaceutical preparations for intratympanal injection are aseptically prepared in hospital pharmacies by using licensed medicinal products as starting material. Recently we developed an updated formulation of dexamethasone dihydrogen phosphate (H₂PO₄) 8 mg/mL/ 0.02% hyaluronic acid injection solution. Hyaluronic acid increases viscosity and enhances diffusion of dexamethasone into the inner ear. As preparation is done in batches for stock, release and stability tests and assessment of shelf life are required. <h3>Aim and Objectives</h3> Preparation process validation and stability testing of ready-to-administer (RTA) dexamethasone H₂PO₄8 mg/mL/ 0.02% hyaluronic acid intratympanal injection solution aseptically prepared by using licensed medicinal products as starting material. <h3>Material and Methods</h3> For a batch of 180 preparations, 100 mL Dexa-ratiopharm 40 mg injection solution (40 mg/5 mL dexamethasone H₂PO₄, water for injection, Na-edetate, NaCl, NaOH) and 2 mL Hyalart (20 mg/2 mL sodium hyaluronate in water for injection, phosphate buffered) were transferred aseptically into an empty infusion bag, mixed, and 0.5 mL each filled into 1 mL Luer plastic syringes, capped, and labelled. 10 mL mixture were transferred into blood culture bottles for rapid sterility testing. Preparations were stored at 2–8 °C and samples withdrawn at day 0, 7, 14, 28, 60, 90. Dexamethasone content and physicochemical stability were determined by quantitative UV-Vis spectroscopy at 238 nm. pH and osmolality were measured in parallel. <h3>Results</h3> Dexamethasone H₂PO₄/hyaluronic acid preparations fulfilled the specifications set. At day 28, the dexamethasone H₂PO₄ concentration amounted to 100.4% ± 0.7% of the initially measured concentration. pH and osmolality of the preparation amounted to stability-improving pH 7.8 and 285 mOsmol/kg, respectively. Both parameters remained unchanged over the observation period. Refrigeration is recommended because of microbiological reasons. <h3>Conclusion and Relevance</h3> The chosen batch-wise preparation process of RTA dexamethasone H₂PO₄8 mg/mL/ 0.02% hyaluronic acid intratympanal injection solution was successfully validated. Stability testing is ongoing and shelf life proven for at least 1 month. <h3>References and/or Acknowledgements</h3> <h3>Conflict of Interest</h3> No conflict of interest