{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,8]],"date-time":"2025-11-08T12:17:18Z","timestamp":1762604238915,"version":"build-2065373602"},"reference-count":40,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2020,11,17]],"date-time":"2020-11-17T00:00:00Z","timestamp":1605571200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Coordena\u00e7\u00e3o de Aperfei\u00e7oamento de Pessoal de N\u00edvel Superior (CAPES\/Brazil), by the Portuguese Science and Technology Foundation (FCT\/MCT) and European Funds (PRODER\/COMPETE)","award":["M-ERA-NET\/0004\/2015 and UIDB\/04469\/2020 (strategic fund)"],"award-info":[{"award-number":["M-ERA-NET\/0004\/2015 and UIDB\/04469\/2020 (strategic fund)"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Crystals"],"abstract":"<jats:p>Amorphous solid dispersions (SDs) containing poorly soluble tamoxifen dispersed in a meth(acrylate) copolymer combination were proposed as a controlled release system. The objective of this work was to investigate the characteristics and performance of the tamoxifen\u2013polymer mixture and evaluate the changes in functionality through a supersaturating dissolution study condition while comparing it to a physical mixture at a fixed drug-loading proportion. Two polymers, Eudragit\u00ae L 100 and Eudragit\u00ae RL 100, were used to prepare SDs with a 1:1 polymer ratio, containing 10%, 20%, or 30% (wt\/wt%) of tamoxifen, by the solvent evaporation method. A physical mixture containing 30% of tamoxifen was also prepared for comparison. SDs were characterized by X-ray diffraction, Fourier-transform infrared spectroscopy, differential scanning calorimetry, and scanning electron microscopy. Dissolution tests were conducted under non-sink conditions to verify the occurrence of drug recrystallization upon its release. Solid-state characterizations confirmed that the drug was in the amorphous state within the polymeric matrix. Tamoxifen release in an acidic medium was mainly affected by the increase in drug concentration caused by the possible loss of interactions that characterize the main polymer functionalities. At pH 7.4, supersaturation was slowly achieved while also contributing to the increase in the kinetic solubility of the drug. The physical mixture demonstrated the best overall performance, suggesting that the polymeric interactions may have negatively affected the drug release. The combination of polymers in the composing SD proved to be a promising strategy to tailor the delivery of poorly soluble drugs. Our study highlights important information on the behavior of tamoxifen as a poorly soluble drug in supersaturating dissolution conditions while released from SD systems.<\/jats:p>","DOI":"10.3390\/cryst10111046","type":"journal-article","created":{"date-parts":[[2020,11,17]],"date-time":"2020-11-17T11:02:12Z","timestamp":1605610932000},"page":"1046","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Enhanced Dissolution Efficiency of Tamoxifen Combined with Methacrylate Copolymers in Amorphous Solid Dispersions"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3872-3813","authenticated-orcid":false,"given":"Dayanne","family":"T. C. da Silva","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Sciences, Federal University of Pernambuco, Av. Prof. Artur de S\u00e1, s\/n, CEP 50740-520 Recife, Brazil"}]},{"given":"Daniela","family":"Nadvorny","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, Federal University of Pernambuco, Av. Prof. Artur de S\u00e1, s\/n, CEP 50740-520 Recife, Brazil"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1526-1572","authenticated-orcid":false,"given":"Lucas J. de A.","family":"Danda","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, Federal University of Pernambuco, Av. Prof. Artur de S\u00e1, s\/n, CEP 50740-520 Recife, Brazil"}]},{"given":"Amanda C. Q. de M.","family":"Vieira","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, Federal University of Pernambuco, Av. Prof. Artur de S\u00e1, s\/n, CEP 50740-520 Recife, Brazil"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6527-6612","authenticated-orcid":false,"given":"Patricia","family":"Severino","sequence":"additional","affiliation":[{"name":"Labora and ry of Nanotechnology and Nanomedicine (LNMED), Institute of Technology and Research (ITP), Tiradentes University, 49010-390 Aracaju, Brazil"},{"name":"Instituto de Tecnologia e Pesquisa (ITP), Av. Murilo Dantas, 300, CEP 49032-490 Aracaju, Brazil"},{"name":"Tiradentes Institute, 150 Mt Vernon St, Dorchester, MA 02125, USA"}]},{"given":"Monica F. La R.","family":"Soares","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, Federal University of Pernambuco, Av. Prof. Artur de S\u00e1, s\/n, CEP 50740-520 Recife, Brazil"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3280-0294","authenticated-orcid":false,"given":"Jos\u00e9 L.","family":"Soares-Sobrinho","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, Federal University of Pernambuco, Av. Prof. Artur de S\u00e1, s\/n, CEP 50740-520 Recife, Brazil"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9737-6017","authenticated-orcid":false,"given":"Eliana B.","family":"Souto","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Technology, Faculty of Pharmacy, University of Coimbra, Polo das Ci\u00eancias da Sa\u00fade Azinhaga de Santa Comba, 3000-548 Coimbra, Portugal"},{"name":"CEB\u2014Centre of Biological Engineering, Campus de Gualtar, University of Minho, 4710-057 Braga, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2020,11,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1053\/j.gastro.2011.09.050","article-title":"Tamoxifen Induces Rapid, Reversible Atrophy, and Metaplasia in Mouse Stomach","volume":"142","author":"Huh","year":"2012","journal-title":"Gastroenterology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"101459","DOI":"10.1016\/j.jddst.2019.101459","article-title":"Manufacturing strategies to develop amorphous solid dispersions: An overview","volume":"55","author":"Mendonsa","year":"2020","journal-title":"J. Drug Deliv. Sci. Technol."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Cho, H.-W., Baek, S.-H., Lee, B.-J., and Jin, H.-E. (2020). Orodispersible Polymer Films with the Poorly Water-Soluble Drug, Olanzapine: Hot-Melt Pneumatic Extrusion for Single-Process 3D Printing. Pharmaceutics, 12.","DOI":"10.3390\/pharmaceutics12080692"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1347","DOI":"10.1016\/j.xphs.2019.12.004","article-title":"Poly (Glycerol Adipate): From a Functionalized Nanocarrier to a Polymeric-Prodrug Matrix to Create Amorphous Solid Dispersions","volume":"109","author":"Gordhan","year":"2020","journal-title":"J. Pharm. Sci."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"739","DOI":"10.1007\/s11095-015-1823-y","article-title":"Dissolution Performance of High Drug Loading Celecoxib Amorphous Solid Dispersions Formulated with Polymer Combinations","volume":"33","author":"Xie","year":"2016","journal-title":"Pharm. Res."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1208\/s12249-009-9240-3","article-title":"Investigations on the Physical Structure and the Mechanism of Drug Release from an Enteric Matrix Microspheres with a Near-Zero-Order Release Kinetics Using SEM and Quantitative FTIR","volume":"10","author":"Obeidat","year":"2009","journal-title":"AAPS PharmSciTech"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1317","DOI":"10.1208\/s12248-015-9825-6","article-title":"Haste Makes Waste: The Interplay Between Dissolution and Precipitation of Supersaturating Formulations","volume":"17","author":"Sun","year":"2015","journal-title":"AAPS J."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/j.ejps.2016.04.001","article-title":"Solubility and dissolution enhancement of efavirenz hot melt extruded amorphous solid dispersions using combination of polymeric blends: A QbD approach","volume":"88","author":"Pawar","year":"2016","journal-title":"Eur. J. Pharm. Sci."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"42141","DOI":"10.1039\/C5RA04756K","article-title":"Bioapplication of graphene oxide derivatives: Drug\/gene delivery, imaging, polymeric modification, toxicology, therapeutics and challenges","volume":"5","author":"Nurunnabi","year":"2015","journal-title":"RSC Adv."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1016\/j.ejps.2016.07.012","article-title":"Modified-chitosan nanoparticles: Novel drug delivery systems improve oral bioavailability of doxorubicin","volume":"93","author":"Khdair","year":"2016","journal-title":"Eur. J. Pharm. Sci."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1016\/j.jconrel.2015.12.024","article-title":"pH-responsive polymer\u2013drug conjugates: Design and progress","volume":"222","author":"Pang","year":"2016","journal-title":"J. Control. Release"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"11791","DOI":"10.1002\/anie.201605892","article-title":"Well-Defined Polymer-Paclitaxel Prodrugs by a Grafting-from-Drug Approach","volume":"55","author":"Louage","year":"2016","journal-title":"Angew. Chem. Int. Ed."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"4555","DOI":"10.1007\/s00289-019-02985-8","article-title":"Development of novel cross-linked carboxymethyl cellulose\/poly(potassium 1-hydroxy acrylate): Synthesis, characterization and properties","volume":"77","author":"Kumar","year":"2019","journal-title":"Polym. Bull."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1016\/j.carbpol.2018.11.085","article-title":"Electrospinning in water and in situ crosslinking of hyaluronic acid \/ cyclodextrin nanofibers: Towards wound dressing with controlled drug release","volume":"207","author":"Couffin","year":"2019","journal-title":"Carbohydr. Polym."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1016\/j.actbio.2013.08.029","article-title":"Effects of crosslinking on the mechanical properties, drug release and cytocompatibility of protein polymers","volume":"10","author":"Martinez","year":"2014","journal-title":"Acta Biomater."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/j.jconrel.2015.06.042","article-title":"Layered superhydrophobic meshes for controlled drug release","volume":"214","author":"Falde","year":"2015","journal-title":"J. Control. Release"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1016\/j.ejpb.2016.08.016","article-title":"An investigation into the use of polymer blends to improve the printability of and regulate drug release from pharmaceutical solid dispersions prepared via fused deposition modeling (FDM) 3D printing","volume":"108","author":"Alhijjaj","year":"2016","journal-title":"Eur. J. Pharm. Biopharm."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1007\/s11094-011-0618-7","article-title":"Interpolymer combinations of chemically complementary grades of Eudragit copolymers: A new direction in the design of peroral solid dosage forms of drug delivery systems with controlled release (review)","volume":"45","author":"Mustafin","year":"2011","journal-title":"Pharm. Chem. J."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.jconrel.2007.09.012","article-title":"Polymer blends for controlled release coatings","volume":"125","author":"Siepmann","year":"2008","journal-title":"J. Control. Release"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1016\/j.ijpharm.2014.09.023","article-title":"Coatings from blends of Eudragit\u00ae RL and L55: A novel approach in pH-controlled drug release","volume":"476","author":"Wulff","year":"2014","journal-title":"Int. J. Pharm."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"104967","DOI":"10.1016\/j.ejps.2019.104967","article-title":"Successful oral delivery of poorly water-soluble drugs both depends on the intraluminal behavior of drugs and of appropriate advanced drug delivery systems","volume":"137","author":"Boyd","year":"2019","journal-title":"Eur. J. Pharm. Sci."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.ejps.2014.01.001","article-title":"Enhanced intestinal permeability and oral bioavailability of enalapril maleate upon complexation with the cationic polymethacrylate Eudragit E100","volume":"55","author":"Olivera","year":"2014","journal-title":"Eur. J. Pharm. Sci."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1016\/j.ijpharm.2013.09.029","article-title":"Poly(meth)acrylate-based coatings","volume":"457","author":"Nollenberger","year":"2013","journal-title":"Int. J. Pharm."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Souto, E.B., Da Da Ana, R., Souto, S.B., Zielinska, A., Marques, C., Andrade, L.N., Horba\u0144czuk, O.K., Atanasov, A.G., Lucarini, M., and Durazzo, A. (2020). In Vitro Characterization, Modelling, and Antioxidant Properties of Polyphenon-60 from Green Tea in Eudragit S100-2 Chitosan Microspheres. Nutrients, 12.","DOI":"10.3390\/nu12040967"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Tambosi, G., Coelho, P.F., Luciano, S., Lenschow, I.C.S., Z\u00e9tola, M., Stulzer, H.K., and Pezzini, B.R. (2018). Challenges to improve the biopharmaceutical properties of poorly water-soluble drugs and the application of the solid dispersion technology. Mat\u00e9ria, 23.","DOI":"10.1590\/s1517-707620180004.0558"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2243","DOI":"10.1007\/s00289-017-2152-6","article-title":"Star-shaped self-assembled micelles of block copolymer [chitosan-co-poly(ethylene glycol) methyl ether methacrylate] hydrogel for hydrophobic drug delivery","volume":"75","author":"Ullah","year":"2017","journal-title":"Polym. Bull."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"406","DOI":"10.1016\/j.eurpolymj.2017.08.032","article-title":"Controlled-release solid dispersions of Eudragit\u00ae FS 100 and poorly soluble spironolactone prepared by electrospinning and melt extrusion","volume":"95","author":"Balogh","year":"2017","journal-title":"Eur. Polym. J."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Tran, T.T., and Tran, P.H.-L. (2019). Controlled Release Film Forming Systems in Drug Delivery: The Potential for Efficient Drug Delivery. Pharmaceutics, 11.","DOI":"10.3390\/pharmaceutics11060290"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1016\/j.ejps.2016.09.033","article-title":"Preparation, characterization and in-vivo evaluation of microemulsions containing tamoxifen citrate anti-cancer drug","volume":"96","author":"Dehghani","year":"2017","journal-title":"Eur. J. Pharm. Sci."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1016\/j.ejpb.2011.12.016","article-title":"Enhanced kinetic solubility profiles of indomethacin amorphous solid dispersions in poly(2-hydroxyethyl methacrylate) hydrogels","volume":"81","author":"Sun","year":"2012","journal-title":"Eur. J. Pharm. Biopharm."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1016\/j.ijpharm.2017.04.021","article-title":"Enhancement of dissolution rate through eutectic mixture and solid solution of posaconazole and benznidazole","volume":"525","author":"Nadvorny","year":"2017","journal-title":"Int. J. Pharm."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/j.molstruc.2007.02.019","article-title":"Vibrational study of tamoxifen citrate polymorphism","volume":"840","author":"Gamberini","year":"2007","journal-title":"J. Mol. Struct."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1016\/j.ijpharm.2016.01.008","article-title":"Continuous preparation of polymer coated drug crystals by solid hollow fiber membrane-based cooling crystallization","volume":"499","author":"Chen","year":"2016","journal-title":"Int. J. Pharm."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"250","DOI":"10.1016\/j.ejpb.2017.02.002","article-title":"Eudragit\u00ae RL as a stabilizer for supersaturation and a substrate for nanocrystal formation","volume":"114","author":"Dereymaker","year":"2017","journal-title":"Eur. J. Pharm. Biopharm."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"2527","DOI":"10.1016\/j.xphs.2015.10.008","article-title":"Polymeric Amorphous Solid Dispersions: A Review of Amorphization, Crystallization, Stabilization, Solid-State Characterization, and Aqueous Solubilization of Biopharmaceutical Classification System Class II Drugs","volume":"105","author":"Baghel","year":"2016","journal-title":"J. Pharm. Sci."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1016\/j.msec.2015.11.019","article-title":"Tamoxifen-loaded poly(L-lactide) nanoparticles: Development, characterization and in vitro evaluation of cytotoxicity","volume":"60","author":"Altmeyer","year":"2016","journal-title":"Mater. Sci. Eng. C"},{"key":"ref_37","first-page":"56","article-title":"Investigation of thermal and viscoelastic properties of polymers relevant to hot melt extrusion\u2014III: Polymethacrylates and polymethacrylic acid based polymers","volume":"5","author":"Parikh","year":"2014","journal-title":"J. Excip. Food Chem."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1327","DOI":"10.1021\/acs.molpharmaceut.8b01261","article-title":"Insights into the Dissolution Mechanism of Ritonavir\u2013Copovidone Amorphous Solid Dispersions: Importance of Congruent Release for Enhanced Performance","volume":"16","author":"Indulkar","year":"2019","journal-title":"Mol. Pharm."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1016\/j.jddst.2018.10.008","article-title":"Understanding the mechanism of dissolution enhancement for poorly water-soluble drugs by solid dispersions containing Eudragit\u00ae E PO","volume":"48","author":"Lin","year":"2018","journal-title":"J. Drug Deliv. Sci. Technol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1021\/acs.molpharmaceut.6b00788","article-title":"Effect of Extent of Supersaturation on the Evolution of Kinetic Solubility Profiles","volume":"14","author":"Han","year":"2016","journal-title":"Mol. Pharm."}],"container-title":["Crystals"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4352\/10\/11\/1046\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T10:34:44Z","timestamp":1760178884000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4352\/10\/11\/1046"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,11,17]]},"references-count":40,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2020,11]]}},"alternative-id":["cryst10111046"],"URL":"https:\/\/doi.org\/10.3390\/cryst10111046","relation":{},"ISSN":["2073-4352"],"issn-type":[{"type":"electronic","value":"2073-4352"}],"subject":[],"published":{"date-parts":[[2020,11,17]]}}}