{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T08:22:00Z","timestamp":1787559720902,"version":"build-2736575974"},"reference-count":46,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T00:00:00Z","timestamp":1787443200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Background\/Objectives: Matrix pellet formulations enable homogeneous incorporation of the active ingredient and advanced control of release depending on the excipients added. The aim of this study was to develop, characterize, and assess the drug release profiles of microcrystalline cellulose (MCC) and isomalt-based matrix pellets with direct drug incorporation, advancing beyond the earlier concept of isomalt as a mere inert core with layered drug application, under simulated physiological conditions in vitro. Methods: Matrix pellets with varying MCC\u2013isomalt ratios (90:10, 70:30, and 50:50) were produced by extrusion\/spheronization and subsequently coated with film-forming polymers. Dissolution experiments were performed under varying osmolarity to characterize release profiles. The experimental design data were statistically evaluated. Results: The extrusion\/spheronization technique yielded uniform, robust matrix pellets with acceptable sphericity and mechanical integrity, even at high isomalt levels. Release from coated pellets was significantly influenced by the polymer coating and osmolarity of the dissolution medium. However, with increasing isomalt content in the matrix, the dependence of drug release kinetics on medium osmolarity was substantially reduced. Conclusions: The production of MCC\u2013isomalt matrix pellets in which isomalt acts as a functional matrix component reduced the effect of osmolarity of dissolution medium on the release of ibuprofen sodium salt in in vitro experiments.<\/jats:p>","DOI":"10.3390\/pharmaceutics18091046","type":"journal-article","created":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T08:03:41Z","timestamp":1787558621000},"page":"1046","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Influence of Core and Membrane Composition on Drug Release from MCC\/Isomalt-Based Matrix Pellets in Biorelevant Osmolarity Media"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7629-1487","authenticated-orcid":false,"given":"Christian","family":"Fleck","sequence":"first","affiliation":[{"name":"Department of Pharmaceutics, Semmelweis University, H\u0151gyes Endre Street 7, 1092 Budapest, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isameddin","family":"Aghrbi","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics, Semmelweis University, H\u0151gyes Endre Street 7, 1092 Budapest, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristina","family":"Vlahovic","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics, Semmelweis University, H\u0151gyes Endre Street 7, 1092 Budapest, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6265-3777","authenticated-orcid":false,"given":"Franciska","family":"Erd\u0151","sequence":"additional","affiliation":[{"name":"Faculty of Information Technology and Bionics, P\u00e1zm\u00e1ny P\u00e9ter Catholic University, Pr\u00e1ter Street 50\/A, 1083 Budapest, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andr\u00e1s J\u00f3zsef","family":"Laki","sequence":"additional","affiliation":[{"name":"Faculty of Information Technology and Bionics, P\u00e1zm\u00e1ny P\u00e9ter Catholic University, Pr\u00e1ter Street 50\/A, 1083 Budapest, Hungary"},{"name":"Department of Biophysics and Radiation Biology, Semmelweis University, T\u0171zolt\u00f3 Street 37-47., 1094 Budapest, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8164-3993","authenticated-orcid":false,"given":"Nikolett","family":"K\u00e1llai-Szab\u00f3","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics, Semmelweis University, H\u0151gyes Endre Street 7, 1092 Budapest, Hungary"},{"name":"Center for Pharmacology and Drug Research & Development, Semmelweis University, \u00dcll\u0151i Street 26., 1085 Budapest, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5434-201X","authenticated-orcid":false,"given":"Istv\u00e1n","family":"Antal","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics, Semmelweis University, H\u0151gyes Endre Street 7, 1092 Budapest, Hungary"},{"name":"Center for Pharmacology and Drug Research & Development, Semmelweis University, \u00dcll\u0151i Street 26., 1085 Budapest, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8865-054X","authenticated-orcid":false,"given":"Mil\u00e9na","family":"Lengyel","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics, Semmelweis University, H\u0151gyes Endre Street 7, 1092 Budapest, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1208\/s12249-010-9396-x","article-title":"Evaluation of Drug Release from Coated Pellets Based on Isomalt, Sugar, and Microcrystalline Cellulose Inert Cores","volume":"11","author":"Luhn","year":"2010","journal-title":"AAPS PharmSciTech"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"K\u00e1llai-Szab\u00f3, N., Lengyel, M., Farkas, D., Barna, \u00c1.T., Fleck, C., Basa, B., and Antal, I. (2022). Review on Starter Pellets: Inert and Functional Cores. Pharmaceutics, 14.","DOI":"10.3390\/pharmaceutics14061299"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"860","DOI":"10.1208\/s12248-014-9611-x","article-title":"Release Behaviour of Single Pellets and Internal Fine 3D Structural Features Co-Define the In Vitro Drug Release Profile","volume":"16","author":"Yang","year":"2014","journal-title":"AAPS J."},{"key":"ref_4","unstructured":"Rowe, R.C., Sheskey, P.J., and Quinn, M.E. (2009). Handbook of Pharmaceutical Excipients, Pharmaceutical Press. [6th ed.]."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Poka, M.S., Milne, M., Wessels, A., and Aucamp, M. (2023). Sugars and Polyols of Natural Origin as Carriers for Solubility and Dissolution Enhancement. Pharmaceutics, 15.","DOI":"10.3390\/pharmaceutics15112557"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Zhang, X., Xing, H., Zhao, Y., and Ma, Z. (2018). Pharmaceutical Dispersion Techniques for Dissolution and Bioavailability Enhancement of Poorly Water-Soluble Drugs. Pharmaceutics, 10.","DOI":"10.3390\/pharmaceutics10030074"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"106704","DOI":"10.1016\/j.ejps.2024.106704","article-title":"Microparticles and Multi-Unit Systems for Advanced Drug Delivery","volume":"194","author":"Farkas","year":"2024","journal-title":"Eur. J. Pharm. Sci."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"101986","DOI":"10.1016\/j.jddst.2020.101986","article-title":"Preparation of Delayed-Release Multiparticulate Formulations of Diclofenac Sodium and Evaluation of Their Dissolution Characteristics Using Biorelevant Dissolution Methods","volume":"60","author":"Zakowiecki","year":"2020","journal-title":"J. Drug Deliv. Sci. Technol."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Zakowiecki, D., Frankiewicz, M., Hess, T., Cal, K., Gajda, M., Dabrowska, J., Kubiak, B., Paszkowska, J., Wiater, M., and Hoc, D. (2021). Development of a Biphasic-Release Multiple-Unit Pellet System with Diclofenac Sodium Using Novel Calcium Phosphate-Based Starter Pellets. Pharmaceutics, 13.","DOI":"10.3390\/pharmaceutics13060805"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1016\/j.jpba.2013.04.026","article-title":"Supramolecular Elucidation of the Quality Attributes of Microcrystalline Cellulose and Isomalt Composite Pellet Cores","volume":"84","author":"Antal","year":"2013","journal-title":"J. Pharm. Biomed. Anal."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1016\/j.powtec.2018.01.077","article-title":"The Influence of Isomalt Particle Morphology on Tabletability after Roll Compaction\/Dry Granulation","volume":"341","author":"Grote","year":"2019","journal-title":"Powder Technol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"118804","DOI":"10.1016\/j.ijpharm.2019.118804","article-title":"New Orodispersible Mini-Tablets for Paediatric Use\u2014A Comparison of Isomalt with a Mannitol Based Co-Processed Excipient","volume":"572","author":"Lura","year":"2019","journal-title":"Int. J. Pharm."},{"key":"ref_13","unstructured":"Bernard, J., Luhn, O., Klebovich, I., Antal, I., and K\u00e1llai, N. (2012). Improved Pharmaceutical Starter Pellets. (Patent WO 2012\/052178 A3)."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/j.ejpb.2021.07.009","article-title":"Influence of the Geometry of 3D Printed Solid Oral Dosage Forms on Their Swallowability","volume":"167","author":"Bogdahn","year":"2021","journal-title":"Eur. J. Pharm. Biopharm."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1016\/j.ejpb.2009.03.005","article-title":"Compaction Properties of Isomalt","volume":"72","author":"Bolhuis","year":"2009","journal-title":"Eur. J. Pharm. Biopharm."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"302","DOI":"10.1016\/j.ejpb.2009.05.007","article-title":"Drug Release from MCC- and Carrageenan-Based Pellets: Experiment and Theory","volume":"73","author":"Kranz","year":"2009","journal-title":"Eur. J. Pharm. Biopharm."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3109\/10837450903460467","article-title":"Development and Evaluation of Controlled Release Ibuprofen Matrix Tablets by Direct Compression Technique","volume":"16","author":"Patel","year":"2011","journal-title":"Pharm. Dev. Technol."},{"key":"ref_18","first-page":"249","article-title":"Formulation and Evaluation of Olanzapine Matrix Pellets for Controlled Release","volume":"19","author":"Gowda","year":"2011","journal-title":"Daru"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1006","DOI":"10.1016\/j.cherd.2010.12.003","article-title":"Delayed Release Matrix Pellet Preparation Containing an Alkalizing Pore-Former Agent","volume":"89","author":"Hamedelniel","year":"2011","journal-title":"Chem. Eng. Res. Des."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1150","DOI":"10.3109\/03639045.2011.562214","article-title":"Non-Coated Multiparticulate Matrix Systems for Colon Targeting","volume":"37","author":"Krenzlin","year":"2011","journal-title":"Drug Dev. Ind. Pharm."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"529","DOI":"10.3109\/02652048.2014.885604","article-title":"Preparation and Evaluation of a Controlled Drug Release of Repaglinide through Matrix Pellets: In Vitro and In Vivo Studies","volume":"31","author":"Tavakoli","year":"2014","journal-title":"J. Microencapsul."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1186\/s43094-021-00374-5","article-title":"Development and Characterization of Multiparticulate System as an Alternative to Unit Dosage Forms Containing Drugs with Diverse Release Profiles","volume":"7","author":"Dhanorkar","year":"2021","journal-title":"Future J. Pharm. Sci."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1016\/j.ijpharm.2011.01.021","article-title":"Mechanistic Modelling of Drug Release from Polymer-Coated and Swelling and Dissolving Polymer Matrix Systems","volume":"418","author":"Kaunisto","year":"2011","journal-title":"Int. J. Pharm."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1016\/S0378-5173(01)00921-8","article-title":"The Influence of Core Materials and Film Coating on the Drug Release from Coated Pellets","volume":"233","author":"Sousa","year":"2002","journal-title":"Int. J. Pharm."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1016\/S0168-3659(02)00143-8","article-title":"Development of Controlled Release Matrix Pellets by Annealing with Micronized Water-Insoluble or Enteric Polymers","volume":"82","author":"Kojima","year":"2002","journal-title":"J. Control. Release"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1016\/S0378-5173(01)00908-5","article-title":"Factors Influencing the Physical Characteristics of Pellets Obtained by Extrusion-Spheronization","volume":"232","author":"Sousa","year":"2002","journal-title":"Int. J. Pharm."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"761","DOI":"10.1248\/cpb.35.761","article-title":"Adsorption of Drugs on Microcrystalline Cellulose Suspended in Aqueous Solutions","volume":"35","author":"Okada","year":"1987","journal-title":"Chem. Pharm. Bull."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1016\/j.ejpb.2008.08.005","article-title":"Production of Pellets via Extrusion\u2013Spheronisation without the Incorporation of Microcrystalline Cellulose: A Critical Review","volume":"71","author":"Thommes","year":"2009","journal-title":"Eur. J. Pharm. Biopharm."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1016\/j.ejpb.2005.10.002","article-title":"Use of \u03ba-Carrageenan as Alternative Pelletisation Aid to Microcrystalline Cellulose in Extrusion\/Spheronisation. I. Influence of Type and Fraction of Filler","volume":"63","author":"Thommes","year":"2006","journal-title":"Eur. J. Pharm. Biopharm."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1016\/j.jpba.2014.06.005","article-title":"Comparative Dissolution Study of Drug and Inert Isomalt Based Core Material from Layered Pellets","volume":"98","author":"Luhn","year":"2014","journal-title":"J. Pharm. Biomed. Anal."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1388","DOI":"10.1021\/mp100149j","article-title":"Physiological Parameters for Oral Delivery and In Vitro Testing","volume":"7","author":"Mudie","year":"2010","journal-title":"Mol. Pharm."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1177","DOI":"10.1002\/jps.21502","article-title":"Postprandial Evolution in Composition and Characteristics of Human Duodenal Fluids in Different Nutritional States","volume":"98","author":"Clarysse","year":"2009","journal-title":"J. Pharm. Sci."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1663","DOI":"10.1007\/s11095-008-9569-4","article-title":"Dissolution Media Simulating Conditions in the Proximal Human Gastrointestinal Tract: An Update","volume":"25","author":"Jantratid","year":"2008","journal-title":"Pharm. Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"2889","DOI":"10.1016\/j.xphs.2017.04.030","article-title":"Osmolality of Orally Administered Solutions Influences Luminal Water Volume and Drug Absorption in Intestine","volume":"106","author":"Ichijo","year":"2017","journal-title":"J. Pharm. Sci."},{"key":"ref_35","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":"ref_36","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1016\/j.ejps.2018.07.015","article-title":"Study on Process Parameters and Optimization of Microencapsulation Based on Phase Separation","volume":"122","author":"Lengyel","year":"2018","journal-title":"Eur. J. Pharm. Sci."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1259","DOI":"10.1002\/jps.2600841022","article-title":"Use of a Power-Consumption-Controlled Extruder in the Development of Pellet Formulations","volume":"84","author":"Kleinebudde","year":"1995","journal-title":"J. Pharm. Sci."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1016\/S0939-6411(02)00015-2","article-title":"The Influence of Pellet Shape and Film Coating on the Filling of Pellets into Hard Shell Capsules","volume":"53","author":"Chopra","year":"2002","journal-title":"Eur. J. Pharm. Biopharm."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"663","DOI":"10.1063\/1.431388","article-title":"Weibull Distribution and Kinetics of Heterogeneous Processes","volume":"63","author":"Kapor","year":"1975","journal-title":"J. Chem. Phys."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1016\/j.jbbm.2006.03.006","article-title":"Investigation on Drug Dissolution and Particle Characteristics of Pellets Related to Manufacturing Process Variables of High-Shear Granulation","volume":"69","author":"Mayer","year":"2006","journal-title":"J. Biochem. Biophys. Methods"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1016\/j.ijpharm.2005.10.044","article-title":"On the Use of the Weibull Function for the Discernment of Drug Release Mechanisms","volume":"309","author":"Papadopoulou","year":"2006","journal-title":"Int. J. Pharm."},{"key":"ref_42","first-page":"e7920","article-title":"Effect of Granules Size on the Release Kinetics of Ibuprofen from Its Matrix Tablet","volume":"9","author":"Akpabio","year":"2022","journal-title":"Open Access Libr. J."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1016\/j.ejpb.2008.12.007","article-title":"Drug Release Mechanisms from Ethylcellulose: PVA-PEG Graft Copolymer-Coated Pellets","volume":"72","author":"Muschert","year":"2009","journal-title":"Eur. J. Pharm. Biopharm."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1016\/0168-3659(90)90160-U","article-title":"Mechanism of Release from Pellets Coated with an Ethylcellulose-Based Film","volume":"14","author":"Ozturk","year":"1990","journal-title":"J. Control. Release"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/j.jconrel.2008.12.003","article-title":"Prediction of Drug Release from Ethylcellulose Coated Pellets","volume":"135","author":"Muschert","year":"2009","journal-title":"J. Control. Release"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1517\/17425247.2013.736962","article-title":"Eudragit\u00ae: A Technology Evaluation","volume":"10","author":"Thakral","year":"2013","journal-title":"Expert Opin. Drug Deliv."}],"container-title":["Pharmaceutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4923\/18\/9\/1046\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T08:04:36Z","timestamp":1787558676000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4923\/18\/9\/1046"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,23]]},"references-count":46,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2026,9]]}},"alternative-id":["pharmaceutics18091046"],"URL":"https:\/\/doi.org\/10.3390\/pharmaceutics18091046","relation":{},"ISSN":["1999-4923"],"issn-type":[{"value":"1999-4923","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,23]]}}}