{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T23:00:18Z","timestamp":1777590018439,"version":"3.51.4"},"reference-count":15,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2026,2,9]],"date-time":"2026-02-09T00:00:00Z","timestamp":1770595200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institutes of Health Institutional Training Grant","award":["T32GM008562"],"award-info":[{"award-number":["T32GM008562"]}]},{"name":"NICHD HELP for NOWS Subaward","award":["3-312-0218259-6716L"],"award-info":[{"award-number":["3-312-0218259-6716L"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Polymers"],"abstract":"<jats:p>Buprenorphine (BUP) is widely used in the treatment of neonatal opioid withdrawal syndrome (NOWS). However, the most compounded formulation contains 30% ethanol, despite regulatory and clinical concerns regarding ethanol exposure in pediatric patients. Thus, this research aimed to develop an ethanol-free sublingual (SL) gel formulation of BUP that would be safe, stable, and suitable for NOWS. Multiple polymers were screened as gelling agents, with hydroxypropyl methylcellulose (HPMC) emerging as the ideal base polymer for the formulation due to its optimal pH, rheological characteristics, and stability. The formulated gels were stored at room temperature and refrigerated conditions for 30 days and evaluated for stability using pH, rheology, and liquid chromatography-mass spectrometry. BUP content was between 90\u2013110% of the labeled amount of the dosage form (75 \u00b5g\/mL) at all time-points, and the pH remained close to physiological values. Release studies demonstrated a drug release of 23\u201324% for SL gels without surfactants stored at room temperature and refrigerated conditions, respectively. Incorporation of non-ionic surfactants (Tween 20 and Tween 80) significantly increased drug release to 33% and 40%, respectively, reflecting enhanced solubilization and improved mucosal penetration. The ethanol-free formulation demonstrated physicochemical stability and favorable release characteristics suitable for neonatal administration. These findings represent a meaningful advance in the development of safer pediatric formulations for NOWS.<\/jats:p>","DOI":"10.3390\/polym18040435","type":"journal-article","created":{"date-parts":[[2026,2,9]],"date-time":"2026-02-09T14:05:15Z","timestamp":1770645915000},"page":"435","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Hydroxypropyl Methylcellulose as a Mucoadhesive Polymer in Ethanol-Free Buprenorphine Gel for Neonatal Sublingual Delivery"],"prefix":"10.3390","volume":"18","author":[{"given":"Sanskruti","family":"Dave","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Sciences, Jefferson College of Pharmacy, Thomas Jefferson University, Philadelphia, PA 19107, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3767-3351","authenticated-orcid":false,"given":"Viren","family":"Soni","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, Jefferson College of Pharmacy, Thomas Jefferson University, Philadelphia, PA 19107, USA"},{"name":"Department of Pharmacology, Physiology & Cancer Biology, Sidney Medical College, Thomas Jefferson University, Philadelphia, PA 19107, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Samarth A.","family":"Shah","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, Jefferson College of Pharmacy, Thomas Jefferson University, Philadelphia, PA 19107, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5074-0141","authenticated-orcid":false,"given":"Walter K.","family":"Kraft","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Physiology & Cancer Biology, Sidney Medical College, Thomas Jefferson University, Philadelphia, PA 19107, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6710-2963","authenticated-orcid":false,"given":"Gagan","family":"Kaushal","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, Jefferson College of Pharmacy, Thomas Jefferson University, Philadelphia, PA 19107, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/j.jpeds.2021.12.021","article-title":"Standardizing the Clinic Definition of Opioid Withdrawal in the Neonate","volume":"243","author":"Jilani","year":"2022","journal-title":"J. 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Bioallied Sci."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"121906","DOI":"10.1016\/j.molliq.2023.121906","article-title":"Interactions between loaded drugs and surfactant molecules in micellar drug delivery systems: A critical review","volume":"382","author":"Saha","year":"2023","journal-title":"J. Mol. Liq."}],"container-title":["Polymers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4360\/18\/4\/435\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,9]],"date-time":"2026-02-09T14:23:22Z","timestamp":1770647002000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4360\/18\/4\/435"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,9]]},"references-count":15,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2026,2]]}},"alternative-id":["polym18040435"],"URL":"https:\/\/doi.org\/10.3390\/polym18040435","relation":{},"ISSN":["2073-4360"],"issn-type":[{"value":"2073-4360","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,9]]}}}