Hospital Pharmacy - June 2020 - 189

836649
research-article2019

HPXXXX10.1177/0018578719836649Hospital PharmacyColsoul et al

Original Article

Long-Term Stability of Lorazepam in
Sodium Chloride 0.9% Stored at Different
Temperatures in Different Containers

Hospital Pharmacy
2020, Vol. 55(3) 189--193
© The Author(s) 2019
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https://doi.org/10.1177/0018578719836649
DOI: 10.1177/0018578719836649
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M. L. Colsoul1, A. Breuer1, N. Goderniaux1, J. D. Hecq1,
L. Soumoy1, B. Bihin1, J. Jamart1, and L. Galanti1

Abstract
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 6 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 3 bottles were stored at 5 ± 3°C and
3 syringes and 3 bottles were stored at room temperature for 30 days. During the storage period, particle appearance or
color change were periodically checked by visual and microscope inspection. Turbidity was assessed by measurements of
optical density (OD) at 3 wavelengths (350 nm, 410 nm, 550 nm). The stability of pH was also evaluated. The lorazepam
concentrations were measured at each time point by high-performance liquid chromatography with ultraviolet detector
at 220 nm. Results: Solutions were physically unstable in syringes at 5 ± 3°C after 4 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 1-sided confidence limit at 95% was below 90% of
the initial concentration. To assess temperature and polypropylene influence, results were compared with 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 form) do not improve the stability.
Keywords
admixture programs/incompatibilities, drug stability, medication therapy management (MTM), psychotherapeutics

Introduction
Lorazepam, a part of the benzodiazepine family, is commonly recommended in the elderly to relieve anxiety and to
produce sedation.1,2 Benzodiazepines modulate positively
the opening of the gamma amino butyric acid (GABA)-A
receptor, a chloride-selective ion channel whose natural
ligand is GABA. The GABA bonding results in a decrease
of excitability of neurons and thus produces a calming effect
on the brain.3
Lorazepam is mainly used in geriatric unit and is gradually administered to the patient by a syringe driver. Currently,
the preparation of syringes at therapeutic concentration is
carried out according to demand by the geriatric staff. To
improve time management and preparations quality, these
infusions could be prepared by a Centralized Intravenous

Additive Service.4,5 However, this goal cannot be achieved
without knowing the infusion stability. Some data are available about the lorazepam stability in glass bottles,6,7 in polyvinyl chloride bags,2,8 in polyolefin bags,2,9 and in
polypropylene syringes.7,10 These data show considerable
variations of lorazepam stability depending on container and
storage temperature. Nevertheless, the long-term stability of
lorazepam diluted in NaCl 0.9% at therapeutic concentration
and stored in syringes at 5 ± 3°C remains unknown. The aim
1

CHU UCL Namur, Yvoir, Belgium

Corresponding Author:
J. D. Hecq, Drug Stability Research Group, CHU UCL Namur, 1 avenue
Therasse, Yvoir 5530, Belgium.
Email: jean-daniel.hecq@uclouvain.be

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