{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,10]],"date-time":"2026-01-10T03:40:52Z","timestamp":1768016452770,"version":"3.49.0"},"reference-count":39,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2022,9,27]],"date-time":"2022-09-27T00:00:00Z","timestamp":1664236800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Universidad Complutense de Madrid","award":["910939"],"award-info":[{"award-number":["910939"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>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 \u00b0C. 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.<\/jats:p>","DOI":"10.3390\/pharmaceutics14102061","type":"journal-article","created":{"date-parts":[[2022,9,28]],"date-time":"2022-09-28T03:30:37Z","timestamp":1664335837000},"page":"2061","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Effect of Primary Packaging Material on the Stability Characteristics of Diazepam and Midazolam Parenteral Formulations"],"prefix":"10.3390","volume":"14","author":[{"given":"Mar\u00eda Jos\u00e9","family":"Rodr\u00edguez Fern\u00e1ndez","sequence":"first","affiliation":[{"name":"Defense Military Pharmacy Center (CEMILFARDEF), Colmenar Viejo, 28770 Madrid, Spain"},{"name":"Quick Identification Laboratory, Military Emergency Unit, Torrej\u00f3n de Ardoz, 28850 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0475-8420","authenticated-orcid":false,"given":"Dolores Remedios","family":"Serrano Lopez","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics, School of Pharmacy, Complutense University of Madrid, 28040 Madrid, Spain"},{"name":"Institute of Industrial Pharmacy, Complutense University of Madrid, 28040 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7823-1904","authenticated-orcid":false,"given":"Juan Jos\u00e9","family":"Torrado","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics, School of Pharmacy, Complutense University of Madrid, 28040 Madrid, Spain"},{"name":"Institute of Industrial Pharmacy, Complutense University of Madrid, 28040 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,9,27]]},"reference":[{"key":"ref_1","first-page":"505","article-title":"Incompatibility of diazepam injection in plastic intravenous bags","volume":"36","author":"Parker","year":"1979","journal-title":"Am. 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