Long-term Physicochemical Stability of Concentrated Solutions of Isosorbide Dinitrate in Polypropylene Syringes for Administration in the Intensive Care Unit

Abstract

In order to avoid fluid overload, more concentrated drug solutions in intensive care units are commonly used. This study evaluated the physicochemical stability of concentrated solution of isosorbide dinitrate in polypropylene syringes during 28 days at 5°C ± 3°C with protection from light. Five syringes of 50 mL, containing 0.60 mg/mL of isosorbide dinitrate in sodium chloride 0.9% were prepared and stored at 5°C ± 3°C with protection from light during 28 days. Immediately after preparation and periodically during the storage, isosorbide dinitrate concentration was measured by an ultra-performance liquid chromatography. Spectrophotometric absorbance at different wavelengths, pH measurements, and microscopic observations were also performed. All solutions were physicochemically stable during the whole period storage at 5°C ± 3°C. No color change, turbidity, precipitation or opacity, significant pH variations, or optic densities were observed in the solutions. Any crystals were seen by microscopic analysis. The concentration of isosorbide dinitrate remained above 90% of the initial concentration during the 28 days of storage. Solutions of isosorbide dinitrate 0.60 mg/mL in syringe of sodium chloride 0.9 % injection can be considered physically and chemically stable for 28 days when stored in syringes at 5°C ± 3°C with protection from light and may be prepared in advance by a centralized intravenous additive service.