{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,18]],"date-time":"2026-10-18T06:36:34Z","timestamp":1792305394632,"version":"4.4.0"},"reference-count":131,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2023,2,7]],"date-time":"2023-02-07T00:00:00Z","timestamp":1675728000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>The aims of this systematic review are to explore the possibilities of using the positron annihilation lifetime spectroscopy (PALS) method in the pharmaceutical industry and to examine the application of PALS as a supportive, predictive method during the research process. In addition, the review aims to provide a comprehensive picture of additional medical and pharmaceutical uses, as the application of the PALS test method is limited and not widely known in this sector. We collected the scientific literature of the last 20 years (2002\u20132022) from several databases (PubMed, Embase, SciFinder-n, and Google Scholar) and evaluated the data gathered in relation to the combination of three directives, namely, the utilization of the PALS method, the testing of solid systems, and their application in the medical and pharmaceutical fields. The application of the PALS method is discussed based on three large groups: substances, drug delivery systems, and medical devices, starting with simpler systems and moving to more complex ones. The results are discussed based on the functionality of the PALS method, via microstructural analysis, the tracking of ageing and microstructural changes during stability testing, the examination of the effects of excipients and external factors, and defect characterization, with a strong emphasis on the benefits of this technique. The review highlights the wide range of possible applications of the PALS method as a non-invasive analytical tool for examining microstructures and monitoring changes; it can be effectively applied in many fields, alone or with complementary testing methods.<\/jats:p>","DOI":"10.3390\/ph16020252","type":"journal-article","created":{"date-parts":[[2023,2,8]],"date-time":"2023-02-08T02:29:08Z","timestamp":1675823348000},"page":"252","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Positron Annihilation Lifetime Spectroscopy as a Special Technique for the Solid-State Characterization of Pharmaceutical Excipients, Drug Delivery Systems, and Medical Devices\u2014A Systematic Review"],"prefix":"10.3390","volume":"16","author":[{"given":"Mariam Majida","family":"Shokoya","sequence":"first","affiliation":[{"name":"University Pharmacy Department of Pharmacy Administration, Semmelweis University, 7-9 H\u0151gyes Street, 1092 Budapest, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3608-6219","authenticated-orcid":false,"given":"Be\u00e1ta-M\u00e1ria","family":"Benk\u0151","sequence":"additional","affiliation":[{"name":"University Pharmacy Department of Pharmacy Administration, Semmelweis University, 7-9 H\u0151gyes Street, 1092 Budapest, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8147-0546","authenticated-orcid":false,"given":"K\u00e1roly","family":"S\u00fcvegh","sequence":"additional","affiliation":[{"name":"Department of Nuclear Chemistry, E\u00f6tv\u00f6s Lor\u00e1nd University, 1518 Budapest, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5419-9137","authenticated-orcid":false,"given":"Rom\u00e1na","family":"Zelk\u00f3","sequence":"additional","affiliation":[{"name":"University Pharmacy Department of Pharmacy Administration, Semmelweis University, 7-9 H\u0151gyes Street, 1092 Budapest, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Istv\u00e1n","family":"Sebe","sequence":"additional","affiliation":[{"name":"University Pharmacy Department of Pharmacy Administration, Semmelweis University, 7-9 H\u0151gyes Street, 1092 Budapest, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,2,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"162507","DOI":"10.1016\/j.nima.2019.162507","article-title":"Positron annihilation lifetime spectroscopy using fast scintillators and digital electronics","volume":"943","author":"Fang","year":"2019","journal-title":"Nucl. Instrum. Methods Phys. Res. Sect. A Accel. Spectrometers Detect. Assoc. Equip."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1016\/j.jpba.2005.07.014","article-title":"Tracking of the physical ageing of amorphous pharmaceutical polymeric excipients by positron annihilation spectroscopy","volume":"40","year":"2006","journal-title":"J. Pharm. Biomed. Anal."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"17527","DOI":"10.1039\/C5CP01921D","article-title":"Positron annihilation lifetime spectroscopy (PALS): A probe for molecular organisation in self-assembled biomimetic systems","volume":"17","author":"Fong","year":"2015","journal-title":"Phys. Chem. Chem. Phys."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"737","DOI":"10.1002\/pen.10461","article-title":"A review of positron annihilation lifetime spectroscopy as applied to the physical aging of polymers","volume":"36","author":"Bigg","year":"1996","journal-title":"Polym. Eng. Sci."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"151901","DOI":"10.1063\/1.4801998","article-title":"Charging-induced defect formation in LixCoO2 battery cathodes studied by positron annihilation spectroscopy","volume":"102","author":"Parz","year":"2013","journal-title":"Appl. Phys. Lett."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1016\/j.jpowsour.2016.10.050","article-title":"First-cycle defect evolution of Li1\u2212xNi1\/3Mn1\/3Co1\/3O2 lithium ion battery electrodes investigated by positron annihilation spectroscopy","volume":"336","author":"Seidlmayer","year":"2016","journal-title":"J. Power Sources"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1016\/j.jpowsour.2014.10.048","article-title":"Insight into cobalt-doping in Li2FeSiO4 cathode material for lithium-ion battery","volume":"274","author":"Zhang","year":"2015","journal-title":"J. Power Sources"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Pagot, G., Toso, V., Barbiellini, B., Ferragut, R., and Di Noto, V. (2021). Positron Annihilation Spectroscopy as a Diagnostic Tool for the Study of LiCoO2 Cathode of Lithium-Ion Batteries. Condens. Matter, 6.","DOI":"10.3390\/condmat6030028"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2006993","DOI":"10.1002\/adma.202006993","article-title":"Porosimetry for Thin Films of Metal\u2013Organic Frameworks: A Comparison of Positron Annihilation Lifetime Spectroscopy and Adsorption-Based Methods","volume":"33","author":"Stassin","year":"2021","journal-title":"Adv. Mater."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"14967","DOI":"10.1021\/acscatal.1c04521","article-title":"Catalyst Deactivation Probed by Positron Annihilation Spectroscopy","volume":"11","author":"Taylor","year":"2021","journal-title":"ACS Catal."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1800268","DOI":"10.1002\/smtd.201800268","article-title":"Shedding New Light on Nanostructured Catalysts with Positron Annihilation Spectroscopy","volume":"2","author":"Mitchell","year":"2018","journal-title":"Small Methods"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"24380","DOI":"10.1021\/acsami.0c05738","article-title":"Influence of Free Volume Determined by Positron Annihilation Lifetime Spectroscopy (PALS) on Gas Permeability of Cellulose Nanocrystal Films","volume":"12","author":"Nuruddin","year":"2020","journal-title":"ACS Appl. Mater. Interfaces"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1357","DOI":"10.1007\/s10570-021-04367-8","article-title":"Water intake of cellulose materials monitored by positron annihilation lifetime spectroscopy","volume":"29","author":"Resch","year":"2022","journal-title":"Cellulose"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Li, J., Laptev, R., Bordulev, I., Siemek, K., Horodek, P., Shen, H., Lomygin, A., and Cui, L. (2022). Positron Annihilation Spectroscopy Study of Metallic Materials after High-Speed Cutting. Materials, 15.","DOI":"10.3390\/ma15031017"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1016\/S0169-4332(99)00203-2","article-title":"Investigation of defects (migration and formation) in metals by positron annihilation lifetime","volume":"149","author":"Badawi","year":"1999","journal-title":"Appl. Surf. Sci."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Klym, H., Karbovnyk, I., Piskunov, S., and Popov, A.I. (2021). Positron Annihilation Lifetime Spectroscopy Insight on Free Volume Conversion of Nanostructured MgAl2O4 Ceramics. Nanomaterials, 11.","DOI":"10.3390\/nano11123373"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"601","DOI":"10.1063\/1.4959021","article-title":"Positron annihilation characterization of free volume in micro- and macro-modified Cu0.4Co0.4Ni0.4Mn1.8O4 ceramics","volume":"42","author":"Klym","year":"2016","journal-title":"Low Temp. Phys."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"110952","DOI":"10.1016\/j.matchar.2021.110952","article-title":"Positron annihilation spectroscopy of defects in nuclear and irradiated materials\u2014A review","volume":"174","author":"Selim","year":"2021","journal-title":"Mater. Charact."},{"key":"ref_19","first-page":"877","article-title":"Positron Annihilation Spectroscopy: Polymer Blends and Miscibility","volume":"Volume 2","author":"Sabu","year":"2014","journal-title":"Characterization of Polymer Blends: Miscibility, Morphology and Interfaces"},{"key":"ref_20","unstructured":"Consolati, G., and Quasso, F. (2010). Polymer Physics: From Suspensions to Nanocomposites and Beyond, Wiley."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/0301-0104(81)80307-2","article-title":"The temperature dependence of positron lifetimes in solid pivalic acid","volume":"63","author":"Eldrup","year":"1981","journal-title":"Chem. Phys."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1016\/S0009-2614(97)00504-6","article-title":"Positronium in large voids. Silicagel","volume":"272","author":"Goworek","year":"1997","journal-title":"Chem. Phys. Lett."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1016\/S0301-0104(98)00068-8","article-title":"Positronium states in the pores of silica gel","volume":"230","author":"Goworek","year":"1998","journal-title":"Chem. Phys."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1016\/S0969-806X(03)00180-4","article-title":"Mesopore characterization by PALS","volume":"68","author":"Goworek","year":"2003","journal-title":"Radiat. Phys. Chem."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Krsjak, V., Degmova, J., Noga, P., Petriska, M., Sojak, S., Saro, M., Neuhold, I., and Slugen, V. (2021). Application of Positron Annihilation Spectroscopy in Accelerator-Based Irradiation Experiments. Materials, 14.","DOI":"10.3390\/ma14216238"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1070\/PU2002v045n01ABEH000971","article-title":"Positron annihilation spectroscopy in materials structure studies","volume":"45","author":"Viktor","year":"2002","journal-title":"Phys.-Uspekhi"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"012014","DOI":"10.1088\/1742-6596\/1253\/1\/012014","article-title":"Determination of positron annihilation lifetime spectroscopy instrument timing resolution function and source terms using standard samples","volume":"1253","author":"Russell","year":"2019","journal-title":"J. Phys. Conf. Ser."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Bailey, D.L., Townsend, D.W., Valk., P.E., and Maisey, M.N. (2005). Positron Emission Tomography: Basic Sciences, Springer.","DOI":"10.1007\/b136169"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Bailey, D.L., Townsend, D.W., Valk., P.E., and Maisey, M.N. (2005). Positron Emission Tomography: Basic Sciences, Springer.","DOI":"10.1007\/b136169"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"275","DOI":"10.4028\/www.scientific.net\/DDF.331.275","article-title":"Applications of Positron Annihilation Spectroscopy to Life Science","volume":"331","author":"Chen","year":"2012","journal-title":"Defect Diffus. Forum"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/j.nima.2010.10.005","article-title":"A simplified digital positron lifetime spectrometer based on a fast digital oscilloscope","volume":"625","author":"Hui","year":"2011","journal-title":"Nucl. Instrum. Methods Phys. Res. Sect. A Accel. Spectrometers Detect. Assoc. Equip."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Nyamweya, N. (2021). Applications of Polymer Blends in Drug Delivery. Future J. Pharm. Sci., 7.","DOI":"10.1186\/s43094-020-00167-2"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1146\/annurev-chembioeng-073009-100847","article-title":"Polymers for Drug Delivery Systems","volume":"1","author":"Liechty","year":"2010","journal-title":"Annu. Rev. Chem. Biomol. Eng."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"9649","DOI":"10.1021\/acs.macromol.1c01258","article-title":"Positron Annihilation Lifetime Spectroscopic Analysis of Plastic Deformation of High-Density Polyethylene","volume":"54","author":"Makarewicz","year":"2021","journal-title":"Macromolecules"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"388","DOI":"10.1016\/j.ejps.2010.07.007","article-title":"Subnanometre size free volumes in amorphous Verapamil hydrochloride: A positron lifetime and PVT study through T(g) in comparison with dielectric relaxation spectroscopy","volume":"41","author":"Dlubek","year":"2010","journal-title":"Eur. J. Pharm. Sci."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1016\/j.saa.2015.04.115","article-title":"Study of chemical bonding, physical and biological effect of metformin drug as an organized medicine for diabetes patients with chromium(III) and vanadium(IV) ions","volume":"149","author":"Adam","year":"2015","journal-title":"Spectrochim. Acta Part A Mol. Biomol. Spectrosc."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1016\/j.apradiso.2015.07.002","article-title":"Positron annihilation lifetime studies of changes in free volume on some biorelevant nitrogen heterocyclic compounds and their S-glycosylation","volume":"105","author":"Mahmoud","year":"2015","journal-title":"Appl. Radiat. Isot."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"2432","DOI":"10.1002\/pssc.200982110","article-title":"Investigation of the free volume in olanzapine by PALS","volume":"6","year":"2009","journal-title":"Phys. Status Solidi C"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"E95","DOI":"10.1208\/pt070495","article-title":"Tracking the physical aging of poly(ethylene oxide): A technical note","volume":"7","author":"Kiss","year":"2006","journal-title":"Aaps Pharmscitech"},{"key":"ref_40","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_41","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1016\/j.jpba.2015.09.030","article-title":"Positron annihilation lifetime study of polyvinylpyrrolidone for nanoparticle-stabilizing pharmaceuticals","volume":"117","author":"Shpotyuk","year":"2016","journal-title":"J. Pharm. Biomed. Anal."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"514","DOI":"10.1016\/S1773-2247(14)50097-4","article-title":"Tracking of the solubility enhancement and drug release stability of melt extrudates containing mebendazole","volume":"24","author":"Sinka","year":"2014","journal-title":"J. Drug Deliv. Sci. Technol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"116931","DOI":"10.1016\/j.carbpol.2020.116931","article-title":"Antiplasticization and phase behavior in phase-separated modified starch-sucrose blends: A positron lifetime and solid-state NMR study","volume":"250","author":"Martini","year":"2020","journal-title":"Carbohydr. Polym."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"319","DOI":"10.4028\/www.scientific.net\/MSF.445-446.319","article-title":"The Depth Profile of Free Volume in Drug Delivery Polymers Studied by Positron Annihilation Spectroscopy","volume":"445\u2013446","author":"Li","year":"2004","journal-title":"Mater. Sci. Forum"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"546","DOI":"10.1016\/j.polymertesting.2012.02.004","article-title":"Real time positron annihilation lifetime spectroscopy for the detection of the hydrocolloid gel-film transition of polymers","volume":"31","year":"2012","journal-title":"Polym. Test."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1619","DOI":"10.1007\/s10570-018-2220-6","article-title":"Microsegregating blends of ethyl cellulose and poly(vinyl pyrrolidone): A combined thermo-mechanical and positron annihilation spectroscopy study","volume":"26","author":"Panzarasa","year":"2019","journal-title":"Cellulose"},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Kelemen, A., Katona, B., M\u00f3dra, S., Aigner, Z., Sebe, I., Pintye-H\u00f3di, K., Zelk\u00f3, R., Regdon, G., and Krist\u00f3, K. (2020). Effects of Sucrose Palmitate on the Physico-Chemical and Mucoadhesive Properties of Buccal Films. Molecules, 25.","DOI":"10.3390\/molecules25225248"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1016\/S0378-5173(02)00317-4","article-title":"Effect of plasticizer on the dynamic surface tension and the free volume of Eudragit systems","volume":"244","author":"Riedl","year":"2002","journal-title":"Int. J. Pharm."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"634","DOI":"10.1016\/j.ijbiomac.2017.12.030","article-title":"Reduction of enthalpy relaxation in gelatine films by addition of polyols","volume":"109","author":"MacNaughtan","year":"2018","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"12643","DOI":"10.1021\/jp074884l","article-title":"Molecular packing in amorphous carbohydrate matrixes","volume":"111","author":"Townrow","year":"2007","journal-title":"J. Phys. Chem. B"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"864","DOI":"10.1021\/bm049355r","article-title":"Carbohydrate polymers in amorphous states: An integrated thermodynamic and nanostructural investigation","volume":"6","author":"Kilburn","year":"2005","journal-title":"Biomacromolecules"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1568","DOI":"10.1021\/jp908462k","article-title":"Specific volume-hole volume correlations in amorphous carbohydrates: Effect of temperature, molecular weight, and water content","volume":"114","author":"Townrow","year":"2010","journal-title":"J. Phys. Chem. B"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1016\/j.radphyschem.2006.03.027","article-title":"The effect of plasticizer on the ageing of Metolose films","volume":"76","author":"Marek","year":"2007","journal-title":"Radiat. Phys. Chem."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1016\/j.ijpharm.2006.01.025","article-title":"Metolose\u2013PEG interaction as seen by positron annihilation spectroscopy","volume":"313","author":"Regdon","year":"2006","journal-title":"Int. J. Pharm."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"9356","DOI":"10.1021\/jp504504p","article-title":"The free volume in dried and H2O-loaded biopolymers studied by positron lifetime measurements","volume":"118","author":"Hugenschmidt","year":"2014","journal-title":"J. Phys. Chem. B"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"2807","DOI":"10.1021\/acs.molpharmaceut.8b00312","article-title":"Effect of Polymer Chain Length on the Physical Stability of Amorphous Drug-Polymer Blends at Ambient Pressure","volume":"15","author":"Jachowicz","year":"2018","journal-title":"Mol. Pharm."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"500","DOI":"10.1007\/s11095-014-1478-0","article-title":"The effect of polymeric excipients on the physical properties and performance of amorphous dispersions: Part I, free volume and glass transition","volume":"32","author":"Li","year":"2015","journal-title":"Pharm. Res."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/j.radphyschem.2013.04.017","article-title":"Effects of excipients on the tensile strength, surface properties and free volume of Klucel\u00ae free films of pharmaceutical importance","volume":"89","author":"Gottnek","year":"2013","journal-title":"Radiat. Phys. Chem."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1016\/j.radphyschem.2019.02.050","article-title":"Preparation and detailed structural characterization of Penicillin G imprinted polymers by PALS and XPS","volume":"159","year":"2019","journal-title":"Radiat. Phys. Chem."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1570","DOI":"10.1016\/j.xphs.2017.02.017","article-title":"New Polyurethane Nail Lacquers for the Delivery of Terbinafine: Formulation and Antifungal Activity Evaluation","volume":"106","author":"Serro","year":"2017","journal-title":"J. Pharm. Sci."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/j.jpba.2013.10.031","article-title":"Drug release profiles and microstructural characterization of cast and freeze dried vitamin B12 buccal films by positron annihilation lifetime spectroscopy","volume":"89","year":"2014","journal-title":"J. Pharm. Biomed. Anal."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"799","DOI":"10.1016\/j.radphyschem.2011.03.002","article-title":"Testing of the structure of macromolecular polymer films containing solid active pharmaceutical ingredient (API) particles","volume":"80","author":"Marek","year":"2011","journal-title":"Radiat. Phys. Chem."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1050","DOI":"10.1016\/j.xphs.2019.10.018","article-title":"Effect of Moisture Sorption on Free Volume and Relaxation of Spray Dried Dispersions: Relation to Drug Recrystallization","volume":"109","author":"Li","year":"2020","journal-title":"J. Pharm. Sci."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1016\/j.reactfunctpolym.2011.01.010","article-title":"On-demand drug delivery from temperature-responsive polyurethane membrane","volume":"71","author":"Chen","year":"2011","journal-title":"React. Funct. Polym."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1016\/j.jpba.2016.07.004","article-title":"Preparation and characterization of nanofibrous sheets for enhanced oral dissolution of nebivolol hydrochloride","volume":"129","author":"Sipos","year":"2016","journal-title":"J. Pharm. Biomed. Anal."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/j.ijpharm.2013.10.011","article-title":"Polymer structure and antimicrobial activity of polyvinylpyrrolidone-based iodine nanofibers prepared with high-speed rotary spinning technique","volume":"458","author":"Sebe","year":"2013","journal-title":"Int. J. Pharm."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.ejps.2018.06.020","article-title":"Microstructural characterization of papaverine-loaded HPC\/PVA gels, films and nanofibers","volume":"122","author":"Kazsoki","year":"2018","journal-title":"Eur. J. Pharm. Sci."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1438","DOI":"10.3109\/03639045.2014.956112","article-title":"Comparison of directly compressed vitamin B12 tablets prepared from micronized rotary-spun microfibres and cast films","volume":"41","author":"Sebe","year":"2015","journal-title":"Drug Dev. Ind. Pharm."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1829","DOI":"10.3109\/03639045.2015.1013967","article-title":"Micro- and macrostructural characterization of polyvinylpirrolidone rotary-spun fibres","volume":"41","author":"Sebe","year":"2015","journal-title":"Drug Dev. Ind. Pharm."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"119740","DOI":"10.1016\/j.ijpharm.2020.119740","article-title":"Development of laboratory-scale high-speed rotary devices for a potential pharmaceutical microfibre drug delivery platform","volume":"588","author":"Sebe","year":"2020","journal-title":"Int. J. Pharm."},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Sipos, E., Csat\u00e1ri, T., Kazsoki, A., Gergely, A., Bitay, E., Szab\u00f3, Z.I., and Zelk\u00f3, R. (2020). Preparation and Characterization of Fenofibrate-Loaded PVP Electrospun Microfibrous Sheets. Pharmaceutics, 12.","DOI":"10.3390\/pharmaceutics12070612"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1016\/j.ijpharm.2017.03.044","article-title":"In vitro and in silico characterization of fibrous scaffolds comprising alternate colistin sulfate-loaded and heat-treated polyvinyl alcohol nanofibrous sheets","volume":"523","author":"Sebe","year":"2017","journal-title":"Int. J. Pharm."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1016\/j.jpba.2015.07.042","article-title":"Tracking of crystalline-amorphous transition of carvedilol in rotary spun microfibres and their formulation to orodispersible tablets for in vitro dissolution enhancement","volume":"115","author":"Sebe","year":"2015","journal-title":"J. Pharm. Biomed. Anal."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1016\/j.jpba.2017.05.035","article-title":"Macro- and microstructural tracking of ageing-related changes of papaverine hydrochloride-loaded electrospun nanofibrous buccal sheets","volume":"143","author":"Kazsoki","year":"2017","journal-title":"J. Pharm. Biomed. Anal."},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Kov\u00e1cs, A., Kazsoki, A., D\u00e9muth, B., Szir\u00e1nyi, B., Madar\u00e1sz, J., S\u00fcvegh, K., and Zelk\u00f3, R. (2020). Influence of Aqueous Solubility-Enhancing Excipients on the Microstructural Characteristics of Furosemide-Loaded Electrospun Nanofibers. Pharmaceutics, 12.","DOI":"10.3390\/pharmaceutics12040385"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"4214","DOI":"10.1021\/acs.molpharmaceut.8b00646","article-title":"Microstructural Distinction of Electrospun Nanofibrous Drug Delivery Systems Formulated with Different Excipients","volume":"15","author":"Kazsoki","year":"2018","journal-title":"Mol. Pharm."},{"key":"ref_77","doi-asserted-by":"crossref","unstructured":"Arany, P., R\u00f3ka, E., Mollet, L., Coleman, A.W., Perret, F., Kim, B., Kov\u00e1cs, R., Kazsoki, A., Zelk\u00f3, R., and Gesztelyi, R. (2019). Fused Deposition Modeling 3D Printing: Test Platforms for Evaluating Post-Fabrication Chemical Modifications and In-Vitro Biological Properties. Pharmaceutics, 11.","DOI":"10.3390\/pharmaceutics11060277"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1016\/j.ijpharm.2012.03.018","article-title":"Tracking of the viability of Stenotrophomonas maltophilia bacteria population in polyvinylalcohol nanofiber webs by positron annihilation lifetime spectroscopy","volume":"429","author":"Vajdai","year":"2012","journal-title":"Int. J. Pharm."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1016\/j.jpba.2014.11.005","article-title":"Microstructural analysis of the fast gelling freeze-dried sodium hyaluronate","volume":"104","author":"Aigner","year":"2015","journal-title":"J. Pharm. Biomed. Anal."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"566","DOI":"10.1016\/j.carbpol.2013.12.003","article-title":"Hydrogen bonding in maltooligomer-glycerol-water matrices: Relation to physical state and molecular free volume","volume":"102","author":"Roussenova","year":"2014","journal-title":"Carbohydr. Polym."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"3237","DOI":"10.1021\/bm1005068","article-title":"Plasticization, antiplasticization, and molecular packing in amorphous carbohydrate-glycerol matrices","volume":"11","author":"Roussenova","year":"2010","journal-title":"Biomacromolecules"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"14278","DOI":"10.1039\/c0cp00681e","article-title":"Characterization of a sucrose\/starch matrix through positron annihilation lifetime spectroscopy: Unravelling the decomposition and glass transition processes","volume":"12","author":"Sharma","year":"2010","journal-title":"Phys. Chem. Chem. Phys."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1016\/j.ejpb.2013.03.036","article-title":"Characterization of dynamics in complex lyophilized formulations: II. Analysis of density variations in terms of glass dynamics and comparisons with global mobility, fast dynamics, and Positron Annihilation Lifetime Spectroscopy (PALS)","volume":"85","author":"Chieng","year":"2013","journal-title":"Eur. J. Pharm. Biopharm."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"530","DOI":"10.1016\/j.xphs.2015.10.004","article-title":"Addition of Monovalent Electrolytes to Improve Storage Stability of Freeze-Dried Protein Formulations","volume":"105","author":"Goshima","year":"2016","journal-title":"J. Pharm. Sci."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1016\/j.ejps.2004.11.009","article-title":"Correlation between the release characteristics of theophylline and the free volume of polyvinylpyrrolidone","volume":"24","year":"2005","journal-title":"Eur. J. Pharm. Sci."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"711","DOI":"10.1016\/j.jpba.2009.01.001","article-title":"Prediction of the stability of polymeric matrix tablets containing famotidine from the positron annihilation lifetime distributions of their physical mixtures","volume":"49","author":"Szente","year":"2009","journal-title":"J. Pharm. Biomed. Anal."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1016\/j.jpba.2009.07.011","article-title":"Correlation between the free volume and the metoprolol tartrate release of Metolose patches","volume":"51","author":"Papp","year":"2010","journal-title":"J. Pharm. Biomed. Anal."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"1096","DOI":"10.1016\/j.xphs.2019.10.058","article-title":"Mechanistic Insights of the Critical Role of Hydrogen Donor in Controlling Drug Release from Acrylate Adhesive","volume":"109","author":"Luo","year":"2020","journal-title":"J. Pharm. Sci."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1016\/j.ijbiomac.2008.09.014","article-title":"The influence of Metolose structure on the free volume and the consequent metoprolol tartrate release of patches","volume":"44","author":"Papp","year":"2009","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"902","DOI":"10.1016\/j.jpba.2010.06.020","article-title":"Tracking of the micro-structural changes of levonorgestrel-releasing intrauterine system by positron annihilation lifetime spectroscopy","volume":"53","author":"Patai","year":"2010","journal-title":"J. Pharm. Biomed. Anal."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1016\/S0969-806X(03)00061-6","article-title":"Positron annihilation study of polyphenylene dendrimers","volume":"67","author":"Marek","year":"2003","journal-title":"Radiat. Phys. Chem."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"3341","DOI":"10.1038\/s41598-022-07200-9","article-title":"Synthesis and defect characterization of hybrid ceria nanostructures as a possible novel therapeutic material towards COVID-19 mitigation","volume":"12","author":"Rocha","year":"2022","journal-title":"Sci. Rep."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"294","DOI":"10.1007\/s11051-016-3605-9","article-title":"Superb hydroxyl radical-mediated biocidal effect induced antibacterial activity of tuned ZnO\/chitosan type II heterostructure under dark","volume":"18","author":"Podder","year":"2016","journal-title":"J. Nanoparticle Res."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"6278","DOI":"10.1039\/c0dt01499k","article-title":"Investigating the binding properties of porous drug delivery systems using nuclear sensors (radiotracers) and positron annihilation lifetime spectroscopy\u2014Predicting conditions for optimum performance","volume":"40","author":"Mume","year":"2011","journal-title":"Dalton Trans."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"686","DOI":"10.1016\/j.saa.2014.04.144","article-title":"Studying functional properties of hydrogel and silicone-hydrogel contact lenses with PALS, MIR and Raman spectroscopy","volume":"131","author":"Filipecki","year":"2014","journal-title":"Spectrochim. Acta Part A Mol. Biomol. Spectrosc."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"31","DOI":"10.17219\/pim\/42721","article-title":"Comparison of Occurrence of Free Volumes for Rigid Gas Permeable and Soft Contact Lenses","volume":"45","author":"Filipecka","year":"2015","journal-title":"Polim. Med."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1016\/j.clae.2010.06.008","article-title":"Void volume variations in contact lens polymers","volume":"34","author":"Sane","year":"2011","journal-title":"Contact Lens Anterior Eye"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"255","DOI":"10.17219\/pim\/33926","article-title":"Study of free volumes of polymer hydrogel and -silicone-hydrogel contact lenses by means of the positron annihilation lifetime spectroscopy method","volume":"44","author":"Filipecki","year":"2014","journal-title":"Polim. Med."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"1837","DOI":"10.1007\/s10856-013-4948-8","article-title":"Structural study of polymer hydrogel contact lenses by means of positron annihilation lifetime spectroscopy and UV-vis-NIR methods","volume":"24","author":"Filipecki","year":"2013","journal-title":"J. Mater. Sci. Mater. Med."},{"key":"ref_100","first-page":"21","article-title":"Structural studies of polymer hydrogel and silicone hydrogel contact lenses by means of positron lifetime spectroscopy methods","volume":"43","author":"Kotynia","year":"2013","journal-title":"Polim. Med."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"17","DOI":"10.17219\/pim\/62279","article-title":"Investigation of the Degree of Disorder of the Structure of Polymer Soft Contact Lenses Using Positron Annihilation Lifetime Spectroscopy PALS","volume":"46","author":"Filipecki","year":"2016","journal-title":"Polim. Med."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"641","DOI":"10.1163\/156856207781034089","article-title":"Glucose and water diffusion kinetics study in a fluorosilicone acrylate contact lens material by positron lifetime spectroscopy","volume":"18","author":"Ranganathaiah","year":"2007","journal-title":"J. Biomater. Sci. Polym. Ed."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"1355","DOI":"10.1007\/s10856-007-3267-3","article-title":"Influence of spoliation in poly(2-hydroxy ethyl methacrylate) soft contact lens on its free volume and optical transparency","volume":"19","author":"Ranganathaiah","year":"2008","journal-title":"J. Mater. Sci. Mater. Med."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1016\/S0969-806X(03)00213-5","article-title":"Positron lifetime studies in vinyl polymers of medical importance","volume":"68","author":"Gordo","year":"2003","journal-title":"Radiat. Phys. Chem."},{"key":"ref_105","first-page":"47","article-title":"Modification influence on the structural parameters of polymer ophthalmic materials","volume":"46","author":"Chamerski","year":"2016","journal-title":"Opt. Appl."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.saa.2017.10.051","article-title":"Spectroscopic studies of the silicone oil impact on the ophthalmic hydrogel based materials conducted in time dependent mode","volume":"192","author":"Chamerski","year":"2018","journal-title":"Spectrochim. Acta Part A Mol. Biomol. Spectrosc."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1016\/j.saa.2016.05.036","article-title":"An investigation of the effect of silicone oil on polymer intraocular lenses by means of PALS, FT-IR and Raman spectroscopies","volume":"167","author":"Chamerski","year":"2016","journal-title":"Spectrochim. Acta Part A Mol. Biomol. Spectrosc."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"21","DOI":"10.17219\/pim\/24548","article-title":"Ageing phenomenon in acrylic polymer dental materials detected by means of positron annihilation lifetime spectroscopy","volume":"44","author":"Filipecki","year":"2014","journal-title":"Polim. Med."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"91","DOI":"10.17219\/pim\/81450","article-title":"Light-cured dimethacrylate dental restorative composites under a prism of annihilating positrons","volume":"47","author":"Shpotyuk","year":"2017","journal-title":"Polim. Med."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"129","DOI":"10.17219\/pim\/68647","article-title":"The Effect of Curing Light Intensity on Free Volume Size in Some Dental Composites","volume":"46","author":"Shirazinia","year":"2016","journal-title":"Polim. Med."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1016\/j.eurpolymj.2010.11.007","article-title":"Characterization of dimethacrylate polymeric networks: A study of the crosslinked structure formed by monomers used in dental composites","volume":"47","author":"Pfeifer","year":"2011","journal-title":"Eur. Polym. J."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"49","DOI":"10.17219\/pim\/118394","article-title":"PALS probing of photopolymerization shrinkage in densely packed acrylate-type dental restorative composites","volume":"49","author":"Shpotyuk","year":"2019","journal-title":"Polim. Med."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"528","DOI":"10.1186\/s11671-016-1751-8","article-title":"Free Volume Structure of Acrylic-Type Dental Nanocomposites Tested with Annihilating Positrons","volume":"11","author":"Shpotyuk","year":"2016","journal-title":"Nanoscale Res. Lett."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"955","DOI":"10.1023\/A:1026346515170","article-title":"Free volume and mechanical properties of Palacos\u00ae R bone cement","volume":"14","author":"Algers","year":"2003","journal-title":"J. Mater. Sci. Mater. Med."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"11","DOI":"10.17219\/pim\/96288","article-title":"A study of the effect of X-ray irradiation on the structure of Narafilcon A biopolymer soft contact lenses","volume":"48","author":"Filipecka","year":"2018","journal-title":"Polim. Med."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1038\/s42254-019-0078-7","article-title":"Positronium in medicine and biology","volume":"1","author":"Moskal","year":"2019","journal-title":"Nat. Rev. Phys."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"428","DOI":"10.1016\/j.ijpharm.2013.01.069","article-title":"Physical aging in pharmaceutical polymers and the effect on solid oral dosage form stability","volume":"457","author":"Kucera","year":"2013","journal-title":"Int. J. Pharm."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/j.ddtec.2018.06.009","article-title":"Matrix systems for oral drug delivery: Formulations and drug release","volume":"27","author":"Veres","year":"2018","journal-title":"Drug Discov. Today Technol."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.addr.2015.12.019","article-title":"Structural and thermodynamic aspects of plasticization and antiplasticization in glassy encapsulation and biostabilization matrices","volume":"100","author":"Ubbink","year":"2016","journal-title":"Adv. Drug. Deliv. Rev."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1007\/s12393-009-9009-1","article-title":"A Review on Methods and Theories to Describe the Glass Transition Phenomenon: Applications in Food and Pharmaceutical Products","volume":"1","author":"Abiad","year":"2009","journal-title":"Food Eng. Rev."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"18","DOI":"10.4103\/2230-973X.96922","article-title":"The effect of water on the solid state characteristics of pharmaceutical excipients: Molecular mechanisms, measurement techniques, and quality aspects of final dosage form","volume":"2","author":"Szakonyi","year":"2012","journal-title":"Int. J. Pharm. Investig."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"5019","DOI":"10.2174\/1381612822666160726094236","article-title":"The Role of Solid State Characterization in Predicting Stability of Solid Dosage Forms","volume":"22","author":"Zelko","year":"2016","journal-title":"Curr. Pharm. Des."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"468","DOI":"10.1016\/j.trac.2016.05.012","article-title":"Lyophilized protein powders: A review of analytical tools for root cause analysis of lot-to-lot variability","volume":"82","author":"Wahl","year":"2016","journal-title":"TrAC Trends Anal. Chem."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1016\/j.addr.2015.05.006","article-title":"Stabilization of proteins in solid form","volume":"93","author":"Cicerone","year":"2015","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1016\/j.partic.2015.06.002","article-title":"Determination of microcapsule physicochemical, structural, and mechanical properties","volume":"24","author":"Gray","year":"2016","journal-title":"Particuology"},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1016\/j.chemphys.2004.12.008","article-title":"Pore structure of silica gel: A comparative study through BET and PALS","volume":"312","author":"Dutta","year":"2005","journal-title":"Chem. Phys."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"4882","DOI":"10.1016\/j.eurpolymj.2007.10.001","article-title":"Microstructure and free volume evaluation of poly(vinyl alcohol) nanocomposite hydrogels","volume":"43","author":"Paranhos","year":"2007","journal-title":"Eur. Polym. J."},{"key":"ref_128","unstructured":"Emmett, S., and Watson, M.J.O.N. (1966). Differential Microcalorimeter. (No. 3,263,484), U.S. Patent."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1016\/S0969-806X(03)00225-1","article-title":"Surface and interfacial effect on polymer glass transition temperature studied by positron annihilation","volume":"68","author":"Zhang","year":"2003","journal-title":"Radiat. Phys. Chem."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"4271","DOI":"10.1016\/j.polymer.2007.05.009","article-title":"Determination of the glass transition temperature of polymer\/layered silicate nanocomposites from positron annihilation lifetime measurements","volume":"48","author":"Kim","year":"2007","journal-title":"Polymer"},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1016\/S0969-806X(99)00243-1","article-title":"Positronium as a tool to monitor changes of chemical structure","volume":"55","author":"Bokor","year":"1999","journal-title":"Radiat. Phys. Chem."}],"container-title":["Pharmaceuticals"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1424-8247\/16\/2\/252\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T18:27:01Z","timestamp":1760120821000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1424-8247\/16\/2\/252"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,2,7]]},"references-count":131,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2023,2]]}},"alternative-id":["ph16020252"],"URL":"https:\/\/doi.org\/10.3390\/ph16020252","relation":{},"ISSN":["1424-8247"],"issn-type":[{"value":"1424-8247","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,2,7]]}}}