Evaluation of Compatibility and Stability of Compounded Otic Solutions Containing Enrofloxacin Over a 20-Day Period.

Abstract

Background: Compounded otic solutions containing enrofloxacin are commonly used in the management of otitis.

Hypothesis/objectives: The study objective was to evaluate the compatibility and stability of enrofloxacin in compounded otic solutions, as determined by physical changes and quantitated strength.

Materials and methods: Twelve solutions containing 100 mg/mL enrofloxacin (Baytril 100; Elanco) or 22.7 mg/mL enrofloxacin (Baytril; Elanco) were quantitatively analysed on Day (D)0, D10, D15, and D20. Both concentrations of enrofloxacin were combined with sterile water (Hospira), tris-EDTA (TrizEDTA; Dechra), sterile water and 4 mg/mL dexamethasone sodium phosphate (dexamethasone, Dexium-SP; Bimeda), tris-EDTA and dexamethasone, tris-EDTA with 0.15% ketoconazole (TrizULTRA Keto; Dechra) and dexamethasone, and 1% miconazole nitrate lotion (Covetrus) and dexamethasone. Gross and microscopic evaluation, pH, and temperature were used to assess physical compatibility. Mass spectrometry was used to evaluate precipitate. High-performance liquid chromatography was used to quantitate drug concentration, indicating strength. Initial separation of ingredients indicating lack of homogenous mixing, immediate precipitate formation, and an exothermic reaction deterred drug strength measurement in solutions containing an antifungal.

Results: On D10, in solutions containing tris-EDTA, average enrofloxacin concentration decreased 25.4% with 100 mg/mL enrofloxacin, 29.3% with 100 mg/mL enrofloxacin and dexamethasone, 45.6% with 22.7 mg/mL enrofloxacin, and 49.8% with 22.7 mg/mL enrofloxacin and dexamethasone. Precipitate formed in all solutions containing tris-EDTA and filtration of the precipitate did not impact the measured enrofloxacin concentration. Compatibility and stability of enrofloxacin were verified in all solutions containing sterile water.

Conclusions and clinical relevance: Clinical use of solutions containing enrofloxacin combined with tris-EDTA or an antifungal is injudicious owing to incompatibility and instability.