{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T10:44:51Z","timestamp":1785149091495,"version":"3.55.0"},"reference-count":49,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2024,8,12]],"date-time":"2024-08-12T00:00:00Z","timestamp":1723420800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Neocaine, LLC. Charlotte, NC, USA","award":["5211540"],"award-info":[{"award-number":["5211540"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Lidocaine hydrochloride (HCl) 2% with 1:100,000 epinephrine (LW\/E) is widely used to prevent pain during dental procedures and has been associated with injection sting, jittering effects, slow onset, and a bitter aftertaste. Since LW\/E\u2019s introduction in 1948, no significant modifications have been proposed. This study aims to design and characterize an improved dental lidocaine HCl injectable formulation without epinephrine (LW\/O\/E) via buffers, sweeteners, and amino acids. LW\/O\/E injections were prepared with pH and osmolality values of 6.5\u20137.0 and 590\u2013610 mOsm\/kg. Using the electronic tongue (ETongue), the LW\/O\/E injectable formulations were characterized for viscosity, injectability, and taste analysis. The results were compared with the LW\/E control. In vivo efficacy and anesthetic duration of the samples were measured through radiant heat tail-flick latency (RHTFL) and hot plate (HP) tests and local toxicity was assessed after a single intra-oral injection in Sprague Dawley rats (SDR). The viscosity and injectability values of the LW\/O\/E samples were found to be comparable to the LW\/E injection. ETongue taste analysis showed an improvement in bitterness reduction of the LW\/O\/E samples compared to the LW\/E formulation. Toxicity studies of samples in SDR showed minor and transient signs of erythema\/eschar and edema. Anesthetic duration via RHTFL and HP paw withdrawal latency time in SDR were found to be comparable for the LW\/O\/E Sample 3A and the LW\/E injection (p &lt; 0.05). In conclusion, the buffered, higher osmolality and reduced bitterness developed LW\/O\/E formulation (Sample 3A) could be considered a promising alternative to the LW\/E formulation for dental use.<\/jats:p>","DOI":"10.3390\/pharmaceutics16081058","type":"journal-article","created":{"date-parts":[[2024,8,12]],"date-time":"2024-08-12T08:54:08Z","timestamp":1723452848000},"page":"1058","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["A Buffered Local Anesthetic Without Epinephrine: Development, Characterization, and In Vivo Efficacy and Toxicity Analysis"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4377-9619","authenticated-orcid":false,"given":"Daniel","family":"Uzbelger Feldman","sequence":"first","affiliation":[{"name":"Department of Endodontology, Temple University Kornberg School of Dentistry, 3223 N. Broad Street, Philadelphia, PA 19140, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-0430-8464","authenticated-orcid":false,"suffix":"II","given":"Billy B.","family":"Laun","sequence":"additional","affiliation":[{"name":"Oral & Maxillofacial Surgery Carbondale, 1111 E. Walnut St Suite B, Carbondale, IL 62901, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chirag","family":"Patel","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, L. M. College of Pharmacy, Ahmedabad 380009, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonal V.","family":"Pande","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, L. M. College of Pharmacy, Ahmedabad 380009, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2513-5879","authenticated-orcid":false,"given":"Sai H. S.","family":"Boddu","sequence":"additional","affiliation":[{"name":"Center of Medical and Bio-allied Health Sciences Research, Ajman University, Ajman P.O. Box 346, United Arab Emirates"},{"name":"Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, Ajman University, Ajman P.O. Box 346, United Arab Emirates"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,8,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1016\/j.cden.2011.02.014","article-title":"Current treatments and advances in pain and anxiety management","volume":"55","author":"Huang","year":"2011","journal-title":"Dent. Clin. N. Am."},{"key":"ref_2","first-page":"11","article-title":"Quantification of patient fears regarding dental injectons and patient perceptions of a local noninjectable anesthetic gel","volume":"26","author":"Crawford","year":"2005","journal-title":"Compend. Contin. Educ. 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