{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T17:19:18Z","timestamp":1788542358027,"version":"build-2803163510"},"reference-count":32,"publisher":"Springer Science and Business Media LLC","issue":"7","license":[{"start":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T00:00:00Z","timestamp":1782777600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"},{"start":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T00:00:00Z","timestamp":1782777600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"}],"funder":[{"DOI":"10.13039\/100000038","name":"U.S. Food and Drug Administration","doi-asserted-by":"publisher","award":["75F40120C00136"],"award-info":[{"award-number":["75F40120C00136"]}],"id":[{"id":"10.13039\/100000038","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Pharm Res"],"published-print":{"date-parts":[[2026,7]]},"DOI":"10.1007\/s11095-026-04117-0","type":"journal-article","created":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T23:44:45Z","timestamp":1782863085000},"page":"2257-2267","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Impact of Mixing Approach and Bubble Formation on In Situ Forming Implant Properties"],"prefix":"10.1007","volume":"43","author":[{"given":"Xinhao","family":"Lin","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seyyed Majid","family":"Eslami","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zixuan","family":"Zhen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong","family":"Yuan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric Wilson","family":"Livingston","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ananya","family":"Aggarwal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mia","family":"Atallah","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andre O\u2019Reilly","family":"Beringhs","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiangnan","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qin","family":"Bin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1961-8156","authenticated-orcid":false,"given":"Xiuling","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,6,30]]},"reference":[{"key":"4117_CR1","doi-asserted-by":"publisher","first-page":"144","DOI":"10.1016\/j.jconrel.2021.06.017","volume":"336","author":"MN O'Brien","year":"2021","unstructured":"O\u2019Brien MN, et al. Challenges and opportunities in the development of complex generic long-acting injectable drug products. J Control Release. 2021;336:144\u201358.","journal-title":"J Control Release"},{"key":"4117_CR2","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1016\/j.jconrel.2013.12.020","volume":"176","author":"RR Thakur","year":"2014","unstructured":"Thakur RR, McMillan HL, Jones DS. Solvent induced phase inversion-based in situ forming controlled release drug delivery implants. J Control Release. 2014;176:8\u201323.","journal-title":"J Control Release"},{"issue":"1","key":"4117_CR3","doi-asserted-by":"publisher","first-page":"4324","DOI":"10.1038\/s41467-019-12141-5","volume":"10","author":"SR Benhabbour","year":"2019","unstructured":"Benhabbour SR, et al. Ultra-long-acting tunable biodegradable and removable controlled release implants for drug delivery. Nat Commun. 2019;10(1):4324.","journal-title":"Nat Commun"},{"issue":"1","key":"4117_CR4","doi-asserted-by":"publisher","first-page":"292","DOI":"10.1016\/j.jconrel.2013.08.024","volume":"172","author":"M Parent","year":"2013","unstructured":"Parent M, et al. PLGA in situ implants formed by phase inversion: critical physicochemical parameters to modulate drug release. J Control Release. 2013;172(1):292\u2013304.","journal-title":"J Control Release"},{"key":"4117_CR5","doi-asserted-by":"publisher","DOI":"10.1016\/j.addr.2021.113912","author":"X Wang","year":"2021","unstructured":"Wang X, Burgess DJ. Drug release from in situ forming implants and advances in release testing. Adv Drug Deliv Rev. 2021. https:\/\/doi.org\/10.1016\/j.addr.2021.113912.","journal-title":"Adv Drug Deliv Rev"},{"key":"4117_CR6","doi-asserted-by":"publisher","DOI":"10.1080\/10837450.2021.1944207","author":"TM Ibrahim","year":"2021","unstructured":"Ibrahim TM, El-Megrab NA, El-Nahas HM. An overview of PLGA in-situ forming implants based on solvent exchange technique: effect of formulation components and characterization. Pharm Dev Technol. 2021. https:\/\/doi.org\/10.1080\/10837450.2021.1944207.","journal-title":"Pharm Dev Technol"},{"issue":"2","key":"4117_CR7","doi-asserted-by":"publisher","first-page":"668","DOI":"10.1016\/j.jconrel.2012.04.016","volume":"161","author":"S Kempe","year":"2012","unstructured":"Kempe S, Mader K. In situ forming implants - an attractive formulation principle for parenteral depot formulations. J Control Release. 2012;161(2):668\u201379.","journal-title":"J Control Release"},{"key":"4117_CR8","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijpharm.2020.120105","volume":"592","author":"MS Suh","year":"2021","unstructured":"Suh MS, et al. Effect of implant formation on drug release kinetics of in situ forming implants. Int J Pharm. 2021;592:120105.","journal-title":"Int J Pharm"},{"key":"4117_CR9","doi-asserted-by":"publisher","DOI":"10.1088\/1748-605X\/ac254c","author":"M Dubar","year":"2021","unstructured":"Dubar M, et al. In-situforming drug-delivery systems for periodontal treatment: current knowledge and perspectives. Biomed Mater. 2021. https:\/\/doi.org\/10.1088\/1748-605X\/ac254c.","journal-title":"Biomed Mater"},{"key":"4117_CR10","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijpharm.2023.122948","volume":"639","author":"X Wang","year":"2023","unstructured":"Wang X, et al. Reverse engineering of Perseris and development of compositionally equivalent formulations. Int J Pharm. 2023;639:122948.","journal-title":"Int J Pharm"},{"issue":"44","key":"4117_CR11","doi-asserted-by":"publisher","first-page":"7468","DOI":"10.1002\/adma.201402509","volume":"26","author":"Y Chen","year":"2014","unstructured":"Chen Y, et al. Injectable smart phase-transformation implants for highly efficient in vivo magnetic-hyperthermia regression of tumors. Adv Mater. 2014;26(44):7468\u201373.","journal-title":"Adv Mater"},{"key":"4117_CR12","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijpharm.2019.118833","volume":"572","author":"M Lizambard","year":"2019","unstructured":"Lizambard M, et al. In-situ forming implants for the treatment of periodontal diseases: simultaneous controlled release of an antiseptic and an anti-inflammatory drug. Int J Pharm. 2019;572:118833.","journal-title":"Int J Pharm"},{"issue":"S1","key":"4117_CR13","doi-asserted-by":"publisher","first-page":"38","DOI":"10.1017\/S109285291900124X","volume":"24","author":"A Krogmann","year":"2019","unstructured":"Krogmann A, et al. Keeping up with the therapeutic advances in schizophrenia: a review of novel and emerging pharmacological entities. CNS Spectr. 2019;24(S1):38\u201369.","journal-title":"CNS Spectr"},{"issue":"2","key":"4117_CR14","doi-asserted-by":"publisher","first-page":"139","DOI":"10.1097\/JAN.0000000000000223","volume":"29","author":"WJ Lorman","year":"2018","unstructured":"Lorman WJ. Sublocade: the once-monthly buprenorphine injectable. J Addict Nurs. 2018;29(2):139\u201340.","journal-title":"J Addict Nurs"},{"key":"4117_CR15","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijpharm.2026.126803","author":"X Lin","year":"2026","unstructured":"Lin X, et al. Formation and degradation process of in situ forming implants \u2013 attributes and impact on performance. Int J Pharm. 2026. https:\/\/doi.org\/10.1016\/j.ijpharm.2026.126803.","journal-title":"Int J Pharm"},{"key":"4117_CR16","doi-asserted-by":"publisher","first-page":"120314","DOI":"10.1016\/j.ijpharm.2021.120314","volume":"597","author":"RG Ingle","year":"2021","unstructured":"Ingle RG, Fang W-J. Prefilled dual chamber devices (DCDs)\u2013promising high-quality and convenient drug delivery system. Int J Pharm. 2021;597:120314.","journal-title":"Int J Pharm"},{"issue":"8","key":"4117_CR17","doi-asserted-by":"publisher","first-page":"2847","DOI":"10.1016\/j.actbio.2009.04.035","volume":"5","author":"MD Krebs","year":"2009","unstructured":"Krebs MD, et al. Injectable poly(lactic-co-glycolic) acid scaffolds with in situ pore formation for tissue engineering. Acta Biomater. 2009;5(8):2847\u201359.","journal-title":"Acta Biomater"},{"key":"4117_CR18","doi-asserted-by":"publisher","first-page":"802","DOI":"10.1016\/j.jconrel.2024.09.045","volume":"375","author":"X Lin","year":"2024","unstructured":"Lin X, et al. Implant dynamics, inner structure, and their impact on drug release of in situ forming implants uncovered through CT imaging. J Control Release. 2024;375:802\u201311.","journal-title":"J Control Release"},{"key":"4117_CR19","doi-asserted-by":"publisher","unstructured":"Lin X, Zhen Z, Eslami SM, Zouabi NA, Ward LE, Darji M, Ranjbar S, Masese FK, Beringhs AO, Kasi RM, Zhang Q. Computed tomography imaging and characteristics of in situ forming implants with different PLGA endcaps.\u00a0Chem Biomed Imaging. 2026 Feb 17. https:\/\/doi.org\/10.1021\/cbmi.6c00001","DOI":"10.1021\/cbmi.6c00001"},{"issue":"6","key":"4117_CR20","doi-asserted-by":"publisher","first-page":"672","DOI":"10.2174\/1389450115666141122211920","volume":"16","author":"H Zhou","year":"2015","unstructured":"Zhou H, et al. Biomedical imaging in implantable drug delivery systems. Curr Drug Targets. 2015;16(6):672\u201382.","journal-title":"Curr Drug Targets"},{"issue":"2","key":"4117_CR21","doi-asserted-by":"publisher","DOI":"10.1208\/s12248-021-00561-5","volume":"23","author":"X Lin","year":"2021","unstructured":"Lin X, O\u2019Reilly Beringhs A, Lu X. Applications of nanoparticle-antibody conjugates in immunoassays and tumor imaging. AAPS J. 2021;23(2):43.","journal-title":"AAPS J"},{"key":"4117_CR22","doi-asserted-by":"publisher","unstructured":"Saha S, Lin X, Zhou L, Xue A, Gosselin E, Chothe PP, Darji M, Lu X, Yang W. Evaluation of the impact of the polymer end groups and molecular weight on in vitro and in vivo performances of PLGA based in situ forming implants for ketoprofen.\u00a0J Pharm Sci. 2025 Jan 1;114(1):424\u201333. https:\/\/doi.org\/10.1016\/j.xphs.2024.10.019","DOI":"10.1016\/j.xphs.2024.10.019"},{"key":"4117_CR23","doi-asserted-by":"publisher","first-page":"146","DOI":"10.1016\/j.jconrel.2020.05.003","volume":"324","author":"S Jeganathan","year":"2020","unstructured":"Jeganathan S, et al. In situ forming implants exposed to ultrasound enhance therapeutic efficacy in subcutaneous murine tumors. J Control Release. 2020;324:146\u201355.","journal-title":"J Control Release"},{"issue":"6","key":"4117_CR24","first-page":"35","volume":"61","author":"TF McDaniel","year":"2013","unstructured":"McDaniel TF, et al. Effects of mixing technique on bubble formation in alginate impression material. Gen Dent. 2013;61(6):35\u20139.","journal-title":"Gen Dent"},{"issue":"6","key":"4117_CR25","doi-asserted-by":"publisher","DOI":"10.3390\/pharmaceutics14061188","volume":"14","author":"JB Joiner","year":"2022","unstructured":"Joiner JB, et al. Effects of drug physicochemical properties on in-situ forming implant polymer degradation and drug release kinetics. Pharmaceutics. 2022;14(6):1188.","journal-title":"Pharmaceutics"},{"key":"4117_CR26","doi-asserted-by":"publisher","DOI":"10.3390\/pharmaceutics16010115","author":"EO Bakhrushina","year":"2024","unstructured":"Bakhrushina EO, et al. Burst release from in situ forming PLGA-based implants: 12 effectors and ways of correction. Pharmaceutics. 2024. https:\/\/doi.org\/10.3390\/pharmaceutics16010115.","journal-title":"Pharmaceutics"},{"issue":"18","key":"4117_CR27","doi-asserted-by":"publisher","DOI":"10.1016\/j.heliyon.2024.e38165","volume":"10","author":"R Sun","year":"2024","unstructured":"Sun R, et al. The drug release of PLGA-based nanoparticles and their application in treatment of gastrointestinal cancers. Heliyon. 2024;10(18):e38165.","journal-title":"Heliyon"},{"key":"4117_CR28","doi-asserted-by":"publisher","DOI":"10.3390\/pharmaceutics14030615","author":"JB Joiner","year":"2022","unstructured":"Joiner JB, et al. Effects of injection volume and route of administration on Dolutegravir in situ forming implant pharmacokinetics. Pharmaceutics. 2022. https:\/\/doi.org\/10.3390\/pharmaceutics14030615.","journal-title":"Pharmaceutics"},{"issue":"3","key":"4117_CR29","doi-asserted-by":"publisher","first-page":"624","DOI":"10.1016\/j.ejpb.2013.03.031","volume":"85","author":"Z Ghalanbor","year":"2013","unstructured":"Ghalanbor Z, K\u00f6rber M, Bodmeier R. Interdependency of protein-release completeness and polymer degradation in PLGA-based implants. Eur J Pharm Biopharm. 2013;85(3):624\u201330.","journal-title":"Eur J Pharm Biopharm"},{"issue":"3","key":"4117_CR30","doi-asserted-by":"publisher","DOI":"10.1088\/2631-7990\/acdd35","volume":"5","author":"A Bandyopadhyay","year":"2023","unstructured":"Bandyopadhyay A, et al. Porous metal implants: processing, properties, and challenges. Int J Extrem Manuf. 2023;5(3):032014.","journal-title":"Int J Extrem Manuf"},{"key":"4117_CR31","doi-asserted-by":"publisher","DOI":"10.1016\/j.xphs.2025.103717","author":"LK Vora","year":"2025","unstructured":"Vora LK, et al. In-situ forming solvent-induced phase inversion implants for controlled drug delivery: role of hydrophilic polymers. J Pharm Sci. 2025. https:\/\/doi.org\/10.1016\/j.xphs.2025.103717.","journal-title":"J Pharm Sci"},{"key":"4117_CR32","doi-asserted-by":"publisher","first-page":"289","DOI":"10.1016\/j.jconrel.2019.07.019","volume":"309","author":"KA Hopkins","year":"2019","unstructured":"Hopkins KA, et al. Noninvasive characterization of in situ forming implant diffusivity using diffusion-weighted MRI. J Control Release. 2019;309:289\u2013301.","journal-title":"J Control Release"}],"container-title":["Pharmaceutical Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s11095-026-04117-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s11095-026-04117-0","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s11095-026-04117-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T17:08:15Z","timestamp":1788541695000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s11095-026-04117-0"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,30]]},"references-count":32,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2026,7]]}},"alternative-id":["4117"],"URL":"https:\/\/doi.org\/10.1007\/s11095-026-04117-0","relation":{},"ISSN":["0724-8741","1573-904X"],"issn-type":[{"value":"0724-8741","type":"print"},{"value":"1573-904X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,30]]},"assertion":[{"value":"10 March 2026","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"4 May 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"30 June 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Xiuling Lu serves on the Editorial Advisory Board of Pharmaceutical Research. The author was not involved in the peer review or editorial decision-making process for this manuscript.","order":1,"name":"Ethics","label":"Conflict of interest","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The views expressed in this article do not reflect the official policies of the U.S. Food and Drug Administration or the U.S. Department of Health and Human Services; nor does any mention of trade names, commercial practices, or organization imply endorsement by the United States Government. This article is subject to FDA public access policy and FDA has the right to make the author accepted manuscript publicly available in PubMed Central upon the official date of publication.","order":2,"name":"Ethics","label":"Disclaimer","group":{"name":"EthicsHeading","label":"Declarations"}}]}}