Stability of Diazepam Solution for Injection Following Long-Term Storage in an Ambient Temperature of the Mediterranean Climate

Itin, Constantin; Liani, Maor; Zur, Meital; Gorenbein, Pavel

doi:10.1007/s11095-020-02984-9

Cited by 3 publications

(2 citation statements)

References 13 publications

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“…Fyllingen et al have reported that after 10 years of storage, less than 1.5% degradation was observed for diazepam injections [ 35 ]. Similar results have recently been reported by Itin et al [ 36 ]. However, for midazolam, Gilliot et al found that at 25 °C, its stability was compromised after 6 months [ 37 ].…”

Section: Discussionsupporting

confidence: 93%

Effect of Primary Packaging Material on the Stability Characteristics of Diazepam and Midazolam Parenteral Formulations

Fernández¹,

Serrano

Torrado

2022

Pharmaceutics

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Diazepam and midazolam are formulated in autoinjectors for parenteral administration to decrease seizures in the case of emergency. However, the compatibility of these lipophilic drugs with the primary packaging material is a key part of drug formulation development. In this work, diazepam and midazolam were packaged in glass syringes as parenteral solutions using two different elastomeric sealing materials (PH 701/50 C BLACK and 4023/50 GRAY). Syringes were stored at three different storage temperatures: 4, 25, and 40 °C. At different time points over 3 years, physical appearance, benzodiazepine sorption on the sealing elastomeric materials, and drug content in solution were assayed. A detailed study on the adsorption profile of both benzodiazepines on the elastomeric gaskets was performed, indicating that the novel rubber material made of bromobutyl derivatives (4023/50 GRAY) is a better choice for manufacturing autoinjectors due to lower drug adsorption. Diazepam showed a better stability profile than midazolam, with the latter solubilised as a hydrochloride salt in an acidic pH that can affect the integrity of the elastomer over time. The amount of drug adsorbed on the surface of the elastomer was measured by NIR and correlated using chemometric models with the amount retained in the elastomeric gaskets quantified by HPLC.

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Section: Discussionsupporting

confidence: 93%

Effect of Primary Packaging Material on the Stability Characteristics of Diazepam and Midazolam Parenteral Formulations

Fernández¹,

Serrano

Torrado

2022

Pharmaceutics

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“…It is unlikely that either compound would mimic the effects of benzodiazepine‐type substances or even be biologically active. No pathological findings were reported in rat studies with 2‐methylamino‐5‐chlorobenzophenone administered intravenously 16 . However, toxicity data on 2‐amino‐3‐(2‐chlorobenzoyl)‐5‐ethylthiophene could not be identified, which means that the health risks associated with its ingestion by unsuspecting people cannot be estimated.…”

Section: Discussionmentioning

confidence: 99%

An unusual detection of 2‐amino‐3‐(2‐chlorobenzoyl)‐5‐ethylthiophene and 2‐methylamino‐5‐chlorobenzophenone in illicit yellow etizolam tablets marked “5617” seized in the Republic of Ireland

Downey¹,

O’Donnell²,

McLaughlin³

et al. 2021

Drug Testing and Analysis

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Benzodiazepines are a class of compounds used clinically to treat a variety of conditions including anxiety and insomnia. Their potential for abuse has led to a surge in their availability on the illegal drugs market. End users often rely on markings on illicit tablets to identify their contents. However, falsified tablets mimicking genuine pharmaceutical preparations often contain ingredients that differ from what people believe they are taking. The absence of any quality control of the content, purity, or strength of fake tablets can result in adverse effects or even fatal outcomes. In recent years, drug seizures involving illicit round yellow tablets marked “5” on one side and “5617” below a scoreline on the reverse have been submitted to Forensic Science Ireland (FSI) by An Garda Síochána (Irish Police) from throughout the Republic of Ireland. These findings relate to 26 different seizures; the cumulative tablet total seized was in excess of 20,000, and the total number of tablets of this description analyzed at FSI was 141. Irish users assume that the active ingredient present was diazepam. The qualitative analytical results for these tablets are reported. All tablets were found to contain 2‐methylamino‐5‐chlorobenzophenone. In addition, the tablets contained either 2‐amino‐3‐(2‐chlorobenzoyl)‐5‐ethylthiophene or etizolam or both. The constituents were present in varying relative amounts in visually similar tablets. Neither 2‐amino‐5‐chlorobenzophenone nor 2‐amino‐3‐(2‐chlorobenzoyl)‐5‐ethylthiophene had previously been found in tablets analyzed at FSI.

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Hot brain: practical climate change advice for neurologists

Sisodiya

2023

Pract Neurol

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‘We are called to be architects of the future, not its victims’—Buckminster FullerPeople with chronic neurological conditions may be vulnerable to change and less able to manage its demands: neurological diseases are among the most burdensome. Whether climate change has particular effects on specific neurological diseases or not, the known impaired resilience to change affecting people with neurological diseases requires neurologists to have awareness of potential climate impacts and their management. Preparedness should include understanding of general national and local alerts and action systems, and the ability to advise patients about managing extreme weather events, particularly heatwaves, but also floods and cold snaps. At the same time, we need more research into the particular consequences of climate change on specific neurological diseases. Climate change is a serious healthcare issue, requiring the neurological community to respond as it would, or did, to other serious challenges, such as COVID-19. As disease experts, we all have a role to play.

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Stability of Diazepam Solution for Injection Following Long-Term Storage in an Ambient Temperature of the Mediterranean Climate

Cited by 3 publications

References 13 publications

Effect of Primary Packaging Material on the Stability Characteristics of Diazepam and Midazolam Parenteral Formulations

Effect of Primary Packaging Material on the Stability Characteristics of Diazepam and Midazolam Parenteral Formulations

An unusual detection of 2‐amino‐3‐(2‐chlorobenzoyl)‐5‐ethylthiophene and 2‐methylamino‐5‐chlorobenzophenone in illicit yellow etizolam tablets marked “5617” seized in the Republic of Ireland

Hot brain: practical climate change advice for neurologists

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