{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,13]],"date-time":"2026-06-13T04:57:00Z","timestamp":1781326620427,"version":"3.54.1"},"reference-count":33,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2026,6,7]],"date-time":"2026-06-07T00:00:00Z","timestamp":1780790400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Polymers"],"abstract":"<jats:p>Phase-inversion in situ implants (PIISIs) represent a versatile polymer platform in which the rational choice of matrix former and solvent system directly governs the macroscopic properties of the resulting depot. This study applied a Quality by Design (QbD) approach to rationalize a bleached shellac\u2013based PIISI, with particular focus on the physicochemical interactions between the polymer and the injection vehicle. Bleached shellac\u2014a natural, low-cost, biodegradable oligomeric resin bearing \u2013COOH, \u2013OH, and ester functional groups\u2014was selected as the matrix former and screened in seven neat solvents and five 1:1 binary combinations at 25% (m\/m). Twelve formulations were evaluated against a predefined set of critical quality attributes, including injectability, phase-inversion kinetics, solvent diffusion volume, and implant structure (n = 5 per formulation; mean \u00b1 standard deviation (SD); one-way analysis of variance (ANOVA) with Tukey\u2019s post hoc test, p &lt; 0.05). Three lead solvent systems\u2014propylene glycol\/N-methylpyrrolidone (PG+NMP), PG\/dimethyl sulfoxide (PG+DMSO), and DMSO\/benzyl alcohol (DMSO+BA)\u2014were identified as those providing an optimal balance between hydrogen-bond donor\/acceptor solvation and controlled solvent extraction. In the second stage, shellac concentration (20\u201335%) was optimized, with 30% shellac in PG+NMP yielding the fastest phase inversion (~50 s), a structurally uniform matrix, and the lowest swelling (22%). A working mechanistic framework consistent with all observed critical quality attribute (CQA) trends in which solvent hydrogen-bond donor\/acceptor balance and water miscibility govern implant architecture is proposed, and it is intended as a hypothesis-generating basis for the rational design of PIISI formulations; direct validation by spectroscopic, thermal-analytical, and biological methods is identified as the next step. The developed formulations are presented as a preliminary physicochemical platform; biological validation (in vitro cytocompatibility and inflammatory response assessment) is required before the system can be considered a validated formulation for dental drug delivery.<\/jats:p>","DOI":"10.3390\/polym18121420","type":"journal-article","created":{"date-parts":[[2026,6,8]],"date-time":"2026-06-08T02:32:46Z","timestamp":1780885966000},"page":"1420","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Phase-Inversion In Situ Implants for Dental Drug Delivery: A QbD-Guided In Vitro Technological Evaluation"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8695-0346","authenticated-orcid":false,"given":"Elena O.","family":"Bakhrushina","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Technology, A.P. Nelyubin Institute of Pharmacy, I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow 119048, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Polina S.","family":"Sakharova","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Technology, A.P. Nelyubin Institute of Pharmacy, I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow 119048, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariya V.","family":"Kotilevskaya","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Technology, A.P. Nelyubin Institute of Pharmacy, I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow 119048, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2866-0049","authenticated-orcid":false,"given":"Iosif B.","family":"Mikhel","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Technology, A.P. Nelyubin Institute of Pharmacy, I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow 119048, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Galina E.","family":"Brkich","sequence":"additional","affiliation":[{"name":"Department of Industrial Pharmacy, I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow 119048, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalya V.","family":"Pyatigorskaya","sequence":"additional","affiliation":[{"name":"Department of Industrial Pharmacy, I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow 119048, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8947-4357","authenticated-orcid":false,"given":"Anzhela S.","family":"Brago","sequence":"additional","affiliation":[{"name":"Department of Propaedeutics of Dental Diseases, Institute of Medicine, Peoples\u2019 Friendship University of Russia Named After Patrice Lumumba, Moscow 117198, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Grigory Yu.","family":"Evzikov","sequence":"additional","affiliation":[{"name":"Department of Nervous Diseases and Neurosurgery, N.V. Sklifosovsky Institute of Clinical Medicine, I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow 119048, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuriy L.","family":"Vasiliev","sequence":"additional","affiliation":[{"name":"Department of Operative Surgery and Topographic Anatomy, N.V. Sklifosovsky Institute of Clinical Medicine, I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow 119048, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"802","DOI":"10.1016\/j.jconrel.2024.09.045","article-title":"Implant Dynamics, Inner Structure, and Their Impact on Drug Release of In Situ Forming Implants Uncovered through CT Imaging","volume":"375","author":"Lin","year":"2024","journal-title":"J. Control. 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