Long-term stability of lorazepam in sodium chloride 0.9% polypropylene syringes at 5±3°C
4 October 2018
A. Breuer1, M.-L. Colsoul1,4, N. Goderniaux1,4, L. Galanti1,4, L. Soumoy2,4, B. Bihin3,4, J. Jamart3,4, J.-D. Hecq2,4 1 Medical Laboratory, CHU UCL Namur, 1 avenue Therasse, 5530 Yvoir, Belgium2 Department of Pharmacy, CHU UCL Namur, 1 avenue Therasse, 5530 Yvoir, Belgium
3 Scientific Support Unit, CHU UCL Namur, 1 avenue Therasse, 5530 Yvoir, Belgium
4 Drug Stability Research Group, CHU UCL Namur, 1 avenue Therasse, 5530 Yvoir, Belgium
Background and objective
Infusion containing lorazepam is used by geriatric department to limit anxiety disorders in the elderly. Currently, these infusions are prepared according to demand by the nursing staff, but the preparation in advance in a centralized service could improve quality of preparation and time management. The aim of this study was to investigate the long-term stability of this infusion in polypropylene syringes stored at 5±3°C. Then, results obtained were compared with stability data of lorazepam in syringes stored at room temperature, glass bottles at 5±3°C and glass bottles at room temperature.
Method
Eight syringes and six bottles of infusion were prepared by diluting 1 ml lorazepam 4 mg in 23 ml of NaCl 0.9% under aseptic conditions. Five syringes and three bottles were stored at 5±3°C and three syringes and three bottles were stored at room temperature for 30 days. During the storage period, particle appearance or colour change were periodically checked by visual and microscope inspection. Turbidity was assessed by measurements of optical density (OD) at three wavelengths (350 nm, 410 nm, 550 nm). pH stability was also evaluated. The lorazepam concentration were measured at each time point by High Performance Liquid Chromatography (HPLC) with UV detector at 220 nm.
Results
Solutions were physically unstable in syringes at 5±3°C after 5 days: crystals and a drop of OD at 350 nm were observed. However, pH was stable. After 2 days, solutions were considered as chemically unstable because a loss of lorazepam concentration higher than 10% was noticed: the lower one-sided confidence limit at 95% was below 90% of the initial concentration. In order to assess temperature and polypropylene influence, results were compared to those obtained for syringes at room temperature and bottles at 5±3°C and room temperature. Precipitation, drop of OD at 350 nm and chemical instability were observed in all conditions.
Conclusion
Solutions of Lorazepam were unstable after 2 days in syringes at 5±3°C. Preparation in advance appears, therefore, not possible for the clinical use. Storage conditions (temperature and container) do not improve the stability.