{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T02:39:26Z","timestamp":1790390366420,"version":"4.1.0"},"reference-count":47,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2019,6,1]],"date-time":"2019-06-01T00:00:00Z","timestamp":1559347200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2019,6,1]],"date-time":"2019-06-01T00:00:00Z","timestamp":1559347200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["European Journal of Pharmaceutics and Biopharmaceutics"],"published-print":{"date-parts":[[2019,6]]},"DOI":"10.1016\/j.ejpb.2019.03.016","type":"journal-article","created":{"date-parts":[[2019,3,19]],"date-time":"2019-03-19T18:43:21Z","timestamp":1553021001000},"page":"142-152","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":56,"special_numbering":"C","title":["Polymer degradation induced drug precipitation in PLGA implants \u2013 Why less is sometimes more"],"prefix":"10.1016","volume":"139","author":[{"given":"Christin","family":"Zlomke","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Barth","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karsten","family":"M\u00e4der","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.ejpb.2019.03.016_b0005","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/0142-9612(96)85754-1","article-title":"Sterilization, toxicity, biocompatibility and clinical applications of polylactic acid\/ polyglycolic acid copolymers","volume":"17","author":"Athanasiou","year":"1996","journal-title":"Biomaterials"},{"key":"10.1016\/j.ejpb.2019.03.016_b0010","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1016\/S0169-409X(97)00048-3","article-title":"Biodegradation and biocompatibility of PLA and PLGA microspheres","volume":"28","author":"Anderson","year":"1997","journal-title":"Adv. Drug Delivery Rev."},{"key":"10.1016\/j.ejpb.2019.03.016_b0015","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1016\/0168-3659(94)90263-1","article-title":"Degradation of poly(D, L-lactic acid) microspheres: effect of molecular weight","volume":"30","author":"Park","year":"1994","journal-title":"J Control Release"},{"key":"10.1016\/j.ejpb.2019.03.016_b0020","doi-asserted-by":"crossref","first-page":"1123","DOI":"10.1016\/0142-9612(95)93575-X","article-title":"Degradation of poly(lactic-co-glycolic acid) microspheres: effect of copolymer composition","volume":"16","author":"Park","year":"1995","journal-title":"Biomaterials"},{"key":"10.1016\/j.ejpb.2019.03.016_b0025","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1002\/jbm.10156","article-title":"Membrane-encased polymer millirods for sustained release of 5-fluorouracil","volume":"61","author":"Qian","year":"2002","journal-title":"J. Biomed. Mater. Res."},{"key":"10.1016\/j.ejpb.2019.03.016_b0030","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1016\/j.ejpb.2008.03.007","article-title":"Effect of formulation parameters on 2-methoxyestradiol release from injectable cylindrical poly(dl-lactide-co-glycolide) implants","volume":"70","author":"Desai","year":"2008","journal-title":"Eur. J. Pharm. Biopharm."},{"key":"10.1016\/j.ejpb.2019.03.016_b0035","doi-asserted-by":"crossref","first-page":"436","DOI":"10.1007\/s11095-013-1173-6","article-title":"Lysozyme release and polymer erosion behavior of injectable implants prepared from PLGA-PEG block copolymers and PLGA\/PLGA-PEG blends","volume":"31","author":"Milacic","year":"2014","journal-title":"Pharm. Res."},{"key":"10.1016\/j.ejpb.2019.03.016_b0040","doi-asserted-by":"crossref","unstructured":"S.K. Plontke, A. Glien, T. Rahne, K. M\u00e4der, A.N. Salt, Controlled release dexamethasone implants in the round window niche for salvage treatment of idiopathic sudden sensorineural hearing loss, Otology & neurotology official publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology 35 (2014) 1168\u20131171.","DOI":"10.1097\/MAO.0000000000000434"},{"key":"10.1016\/j.ejpb.2019.03.016_b0045","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/j.heares.2018.03.006","article-title":"Controlled drug release to the inner ear: concepts, materials, mechanisms, and performance","volume":"368","author":"M\u00e4der","year":"2018","journal-title":"Hearing Res."},{"key":"10.1016\/j.ejpb.2019.03.016_b0050","doi-asserted-by":"crossref","first-page":"139","DOI":"10.2174\/156720212800410894","article-title":"Cisternal sustained release dihydropyridines for subarachnoid hemorrhage","volume":"9","author":"Cook","year":"2012","journal-title":"CNR"},{"key":"10.1016\/j.ejpb.2019.03.016_b0055","series-title":"Cerebral Vasospasm: Neurovascular Events After Subarachnoid Hemorrhage","first-page":"41","article-title":"Development of Nicardipine Prolonged-Release Implants After Clipping for Preventing Cerebral Vasospasm: From Laboratory to Clinical Trial","author":"Kasuya","year":"2013"},{"key":"10.1016\/j.ejpb.2019.03.016_b0060","first-page":"895","article-title":"Application of nicardipine prolonged-release implants: Analysis of 97 consecutive patients with acute subarachnoid hemorrhage","volume":"56","author":"Kasuya","year":"2005","journal-title":"Neurosurgery"},{"key":"10.1016\/j.ejpb.2019.03.016_b0065","doi-asserted-by":"crossref","first-page":"330","DOI":"10.1161\/01.STR.0000254601.74596.0f","article-title":"Effect of nicardipine prolonged-release implants on cerebral vasospasm and clinical outcome after severe aneurysmal subarachnoid hemorrhage: a prospective randomized, double-blind phase IIa study","volume":"38","author":"Barth","year":"2007","journal-title":"Stroke"},{"key":"10.1016\/j.ejpb.2019.03.016_b0070","unstructured":"J. Breitenbach, B. Liepold, D.R. Lefebvre, S. Bossmann, B. Steitz, P. H\u00f6lig, Delivery system for sustained release of a calcium-channel blocking agent, EP 2 308 478 A1 (2011)."},{"key":"10.1016\/j.ejpb.2019.03.016_b0075","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1016\/j.ijpharm.2011.05.049","article-title":"The mechanisms of drug release in poly(lactic-co-glycolic acid)-based drug delivery systems\u2013a review","volume":"415","author":"Fredenberg","year":"2011","journal-title":"Int. J. Pharm."},{"key":"10.1016\/j.ejpb.2019.03.016_b0080","first-page":"123","article-title":"Structure-property relationships in the case of the degradation of massive aliphatic poly-(alpha-hydroxy acids) in aqueous media: Part 1: Poly(DL-lactic acid)","volume":"1","author":"Li","year":"1990","journal-title":"J. Mater. Sci.: Mater. Med."},{"key":"10.1016\/j.ejpb.2019.03.016_b0085","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1016\/0142-9612(96)89664-5","article-title":"Non-invasive in vivo characterization of release processes in biodegradable polymers by low-frequency electron paramagnetic resonance spectroscopy","volume":"17","author":"M\u00e4der","year":"1996","journal-title":"Biomaterials"},{"key":"10.1016\/j.ejpb.2019.03.016_b0090","first-page":"131","article-title":"Structure-property relationships in the case of the degradation of massive poly(alpha-hydroxy acids) in aqueous media: Part 2 Degradation of lactide-glycolide copolymers: PLA37.5GA25 and PLA75GA25","volume":"1","author":"Li","year":"1990","journal-title":"J. Mater. Sci.: Mater. Med."},{"key":"10.1016\/j.ejpb.2019.03.016_b0095","doi-asserted-by":"crossref","first-page":"819","DOI":"10.1002\/jps.2600781008","article-title":"Evaluation of biodegradable poly(lactide) pellets prepared by direct compression","volume":"78","author":"Bodmeier","year":"1989","journal-title":"J. Pharm. Sci."},{"key":"10.1016\/j.ejpb.2019.03.016_b0100","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/j.ijpharm.2007.10.030","article-title":"PLGA-based drug delivery systems: Importance of the type of drug and device geometry","volume":"354","author":"Klose","year":"2008","journal-title":"Int J Pharm"},{"key":"10.1016\/j.ejpb.2019.03.016_b0105","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1016\/j.ijpharm.2005.07.030","article-title":"Effects of the type of release medium on drug release from PLGA-based microparticles: experiment and theory","volume":"314","author":"Faisant","year":"2006","journal-title":"Int. J. Pharm."},{"key":"10.1016\/j.ejpb.2019.03.016_b0110","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/j.ijpharm.2010.10.054","article-title":"Unintended potential impact of perfect sink conditions on PLGA degradation in microparticles","volume":"404","author":"Klose","year":"2011","journal-title":"Int. J. Pharm"},{"key":"10.1016\/j.ejpb.2019.03.016_b0115","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.ijpharm.2012.04.053","article-title":"Impact of the experimental conditions on drug release from parenteral depot systems: From negligible to significant","volume":"432","author":"Delplace","year":"2012","journal-title":"Int. J. Pharm."},{"key":"10.1016\/j.ejpb.2019.03.016_b0120","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1016\/j.ejpb.2006.06.009","article-title":"Effect of drug type on the degradation rate of PLGA matrices","volume":"64","author":"Siegel","year":"2006","journal-title":"Eur. J. Pharm. Biopharm."},{"key":"10.1016\/j.ejpb.2019.03.016_b0125","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1016\/S0378-5173(98)00133-1","article-title":"The effects of drug physico-chemical properties on release from copoly (lactic\/glycolic acid) matrix","volume":"169","author":"Miyajima","year":"1998","journal-title":"Int. J. Pharm."},{"key":"10.1016\/j.ejpb.2019.03.016_b0130","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1016\/S0168-3659(99)00149-2","article-title":"Effect of polymer\/basic drug interactions on the two-stage diffusion-controlled release from a poly(l-lactic acid) matrix","volume":"61","author":"Miyajima","year":"1999","journal-title":"J. Control. Rel."},{"key":"10.1016\/j.ejpb.2019.03.016_b0135","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/0168-3659(95)00138-7","article-title":"Hydrolytic degradation of poly(dl-lactic acid) in the presence of caffeine base","volume":"40","author":"Li","year":"1996","journal-title":"J Control Release"},{"key":"10.1016\/j.ejpb.2019.03.016_b0140","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1016\/S0168-3659(00)00305-9","article-title":"Mechanistic aspects of the release of levamisole hydrochloride from biodegradable polymers","volume":"69","author":"Gallagher","year":"2000","journal-title":"J. Control Release"},{"key":"10.1016\/j.ejpb.2019.03.016_b0145","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1016\/j.jconrel.2004.10.019","article-title":"Controlled release from bioerodible polymers: effect of drug type and polymer composition","volume":"102","author":"Frank","year":"2005","journal-title":"J. Control. Release Off. J. Control. Release Soc."},{"key":"10.1016\/j.ejpb.2019.03.016_b0150","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/S0168-3659(96)01469-1","article-title":"In vitro evaluation of the hydrolytic degradation of dispersed and aggregated poly(dl-lactide-co-glycolide) microspheres","volume":"43","author":"Sansdrap","year":"1997","journal-title":"J. Control Release"},{"key":"10.1016\/j.ejpb.2019.03.016_b0155","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/j.ejpb.2012.12.016","article-title":"In situ forming nimodipine depot system based on microparticles for the treatment of posthemorrhagic cerebral vasospasm","volume":"84","author":"Bege","year":"2013","journal-title":"Eur. J. Pharm. Biopharm."},{"key":"10.1016\/j.ejpb.2019.03.016_b0160","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0042597","article-title":"Local delivery of nimodipine by prolonged-release microparticles\u2014feasibility, effectiveness and dose-finding in experimental subarachnoid hemorrhage","volume":"7","author":"H\u00e4nggi","year":"2012","journal-title":"PLoS ONE"},{"key":"10.1016\/j.ejpb.2019.03.016_b0165","unstructured":"EDGE Therapeutics, Pipeline EG-1962, http:\/\/www.edgetherapeutics.com\/pipeline\/#eg-1962."},{"key":"10.1016\/j.ejpb.2019.03.016_b0170","doi-asserted-by":"crossref","first-page":"512","DOI":"10.1002\/1097-4636(20010615)55:4<512::AID-JBM1044>3.0.CO;2-N","article-title":"Fabrication and characterization of controlled release poly(D, L-lactide-co-glycolide) millirods","volume":"55","author":"Qian","year":"2001","journal-title":"J. Biomed. Mater. Res."},{"key":"10.1016\/j.ejpb.2019.03.016_b0175","unstructured":"Evonik Industries AG, RESOMER\u00ae product portfolio, http:\/\/www.resomer.com\/product\/biodegradable-polymers\/en\/pharma-polymers\/products\/pages\/bioresorbable-polymer.aspx, accessed 29 August 2016."},{"key":"10.1016\/j.ejpb.2019.03.016_b0180","article-title":"PLGA nanoparticles for peroral delivery: How important is pancreatic digestion and can we control it?","author":"Mante","year":"2016","journal-title":"Eur. J. Pharm. Biopharm. off. Journal Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V"},{"key":"10.1016\/j.ejpb.2019.03.016_b0185","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.jconrel.2005.07.009","article-title":"Plasticizing effect of water on poly(lactide-co-glycolide)","volume":"108","author":"Blasi","year":"2005","journal-title":"J. Control. Release Off. J. Control. Release Soc."},{"key":"10.1016\/j.ejpb.2019.03.016_b0190","doi-asserted-by":"crossref","first-page":"813","DOI":"10.1016\/S0142-9612(03)00597-0","article-title":"Study of the initial stages of drug release from a degradable matrix of poly(d, l-lactide-co-glycolide)","volume":"25","author":"Frank","year":"2004","journal-title":"Biomaterials"},{"key":"10.1016\/j.ejpb.2019.03.016_b0195","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1016\/j.jconrel.2010.11.020","article-title":"Pore formation and pore closure in poly(D, L-lactide-co-glycolide) films","volume":"150","author":"Fredenberg","year":"2011","journal-title":"J. Control. Release Off. J. Control. Release Soc."},{"key":"10.1016\/j.ejpb.2019.03.016_b0200","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1016\/0168-3659(89)90047-3","article-title":"The acceleration of degradation-controlled drug delivery from polyester microspheres","volume":"8","author":"Cha","year":"1989","journal-title":"J. Control. Release"},{"key":"10.1016\/j.ejpb.2019.03.016_b0205","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/0378-5173(89)90068-9","article-title":"The effect of the addition of low molecular weight poly(dl-lactide) on drug release from biodegradable poly(dl-lactide) drug delivery systems","volume":"51","author":"Bodmeier","year":"1989","journal-title":"Int. J. Pharm."},{"key":"10.1016\/j.ejpb.2019.03.016_b0210","doi-asserted-by":"crossref","first-page":"2581","DOI":"10.1002\/jps.21287","volume":"97","author":"Shalaeva","year":"2008","journal-title":"J. Pharm. Sci."},{"key":"10.1016\/j.ejpb.2019.03.016_b0215","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1016\/j.jconrel.2004.03.018","article-title":"Anomalous dissolution behaviour of tablets prepared from sugar glass-based solid dispersions","volume":"97","author":"van Drooge","year":"2004","journal-title":"J. Control. Release Off. J. Control. Release Soc."},{"key":"10.1016\/j.ejpb.2019.03.016_b0220","doi-asserted-by":"crossref","first-page":"2365","DOI":"10.1021\/acs.molpharmaceut.5b00056","article-title":"pH-Dependent liquid-liquid phase separation of highly supersaturated solutions of weakly basic drugs","volume":"12","author":"Indulkar","year":"2015","journal-title":"Molec. Pharm."},{"key":"10.1016\/j.ejpb.2019.03.016_b0225","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1021\/mp100251s","article-title":"Polymorphs and solvates of nicardipine hydrochloride, Selective stabilization of different diastereomeric racemates","volume":"8","author":"Moreno-Calvo","year":"2011","journal-title":"Molec. Pharm."},{"key":"10.1016\/j.ejpb.2019.03.016_b0230","doi-asserted-by":"crossref","first-page":"1418","DOI":"10.1002\/jps.2600831011","article-title":"Solubilization of nicardipine hydrochloride via complexation and salt formation","volume":"83","author":"Maurin","year":"1994","journal-title":"J. Pharm. Sci."},{"key":"10.1016\/j.ejpb.2019.03.016_b0235","doi-asserted-by":"crossref","first-page":"1011","DOI":"10.1227\/01.NEU.0000327574.32000.9A","article-title":"Treatment of cerebral vasospasm with biocompatible controlled-release systems for intracranial drug delivery","volume":"63","author":"Omeis","year":"2008","journal-title":"Neurosurgery"}],"container-title":["European Journal of Pharmaceutics and Biopharmaceutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0939641118308440?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0939641118308440?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,10,15]],"date-time":"2025-10-15T16:34:08Z","timestamp":1760546048000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0939641118308440"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,6]]},"references-count":47,"alternative-id":["S0939641118308440"],"URL":"https:\/\/doi.org\/10.1016\/j.ejpb.2019.03.016","relation":{},"ISSN":["0939-6411"],"issn-type":[{"value":"0939-6411","type":"print"}],"subject":[],"published":{"date-parts":[[2019,6]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Polymer degradation induced drug precipitation in PLGA implants \u2013 Why less is sometimes more","name":"articletitle","label":"Article Title"},{"value":"European Journal of Pharmaceutics and Biopharmaceutics","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.ejpb.2019.03.016","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2019 Elsevier B.V. All rights reserved.","name":"copyright","label":"Copyright"}]}}