{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T03:13:22Z","timestamp":1792034002201,"version":"4.4.0"},"reference-count":45,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2023,1,11]],"date-time":"2023-01-11T00:00:00Z","timestamp":1673395200000},"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>One of the main challenges to paediatric drug administration is swallowing difficulties, hindering the acceptability of the medicine and hence clinical outcomes. This study aims at developing a child-appropriate dosage form, the orodispersible mini-tablet (ODMT), using the model drug carbamazepine (CBZ). This dosage form was prepared and 3D-printed via a semi-solid extrusion technique. Design of Experiment methods were applied for optimising the formulation. The formulation with 40% (w\/w) of SSG (superdisintegrant) and 5% (w\/w) of PVP K30 (binder) was selected and loaded with CBZ. The drug-loaded tablets were characterised by a mean hardness of 18.5 N and a disintegrating time of 84 s, along with acceptable friability. The mean drug loading ratio of the tablets was tested as 90.56%, and the drug release rate in 0.1 M HCl reached 68.3% at 45 min. Excipients showed proper compatibility with the drug in physical form analysis. Taste assessment via an E-tongue was also conducted, where the drug did not show bitter taste signals at a low concentration in the taste assessment, and the sweetener also blocked bitterness signals in the testing. To this end, ODMTs were found to be potential candidates for child-appropriate dosage forms delivering CBZ.<\/jats:p>","DOI":"10.3390\/pharmaceutics15010250","type":"journal-article","created":{"date-parts":[[2023,1,12]],"date-time":"2023-01-12T02:28:44Z","timestamp":1673490524000},"page":"250","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":38,"title":["Formulation and Characterisation of Carbamazepine Orodispersible 3D-Printed Mini-Tablets for Paediatric Use"],"prefix":"10.3390","volume":"15","author":[{"given":"Jiayu","family":"Hu","sequence":"first","affiliation":[{"name":"Pharmaceutics Department, School of Pharmacy, University College London, 29-39 Brunswick Square, London WC1N 1AX, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4309-2155","authenticated-orcid":false,"given":"Rawan","family":"Fitaihi","sequence":"additional","affiliation":[{"name":"Pharmaceutics Department, School of Pharmacy, University College London, 29-39 Brunswick Square, London WC1N 1AX, UK"},{"name":"Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shorooq","family":"Abukhamees","sequence":"additional","affiliation":[{"name":"Pharmaceutics Department, School of Pharmacy, University College London, 29-39 Brunswick Square, London WC1N 1AX, UK"},{"name":"Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmaceutical Sciences, The Hashemite University, Zarqa 13115, Jordan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8344-2431","authenticated-orcid":false,"given":"Hend E.","family":"Abdelhakim","sequence":"additional","affiliation":[{"name":"Pharmaceutics Department, School of Pharmacy, University College London, 29-39 Brunswick Square, London WC1N 1AX, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,1,11]]},"reference":[{"key":"ref_1","unstructured":"European Medicines Agency (2022, August 22). Guideline on Pharmaceutical Development of Medicines for Paediatric Use. Available online: https:\/\/www.ema.europa.eu\/en\/documents\/scientific-guideline\/guideline-pharmaceutical-development-medicines-paediatric-use_en.pdf."},{"key":"ref_2","unstructured":"European Medicines Agency (2022, August 22). Rewards and Incentives for Paediatric Medicines. Available online: https:\/\/www.ema.europa.eu\/en\/human-regulatory\/research-development\/paediatric-medicines\/rewards-incentives-paediatric-medicines."},{"key":"ref_3","unstructured":"European Medicines Agency (2022, August 22). Paediatric Investigation Plans. Available online: https:\/\/www.ema.europa.eu\/en\/human-regulatory\/research-development\/paediatric-medicines\/paediatric-investigation-plans."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"902","DOI":"10.1080\/10837450.2019.1615090","article-title":"Orally disintegrating tablets and orally disintegrating mini tablets\u2014Novel dosage forms for pediatric use","volume":"24","author":"Comoglu","year":"2019","journal-title":"Pharm. Dev. Technol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1208\/s12249-016-0558-3","article-title":"Paediatric drug development and formulation design-a European perspective","volume":"18","author":"Kozarewicz","year":"2017","journal-title":"AAPS PharmSciTech"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1871","DOI":"10.1007\/s40265-014-0297-2","article-title":"Patient-centered pharmaceutical design to improve acceptability of medicines: Similarities and differences in paediatric and geriatric populations","volume":"74","author":"Liu","year":"2014","journal-title":"Drugs"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"S26","DOI":"10.1002\/jcph.1138","article-title":"Drug formulations: Standards and novel strategies for drug administration in pediatrics","volume":"58","author":"Thabet","year":"2018","journal-title":"J. Clin. Pharmacol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"462","DOI":"10.1016\/j.ejpb.2011.02.005","article-title":"Orally disintegrating mini-tablets (ODMTs)\u2014A novel solid oral dosage form for paediatric use","volume":"78","author":"Stoltenberg","year":"2011","journal-title":"Eur. J. Pharm. Biopharm."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2","DOI":"10.4103\/0976-9668.71663","article-title":"Orodispersible tablets: A new trend in drug delivery","volume":"1","author":"Dey","year":"2010","journal-title":"J. Nat. Sci. Biol. Med."},{"key":"ref_10","unstructured":"Bandari, S., Mittapalli, R.K., and Gannu, R. (2014). Orodispersible tablets: An overview. Asian J. Pharm., 2."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1515\/acph-2015-0038","article-title":"Risperidone oral disintegrating mini-tablets: A robust-product for pediatrics","volume":"65","author":"Ahmed","year":"2015","journal-title":"Acta Pharm."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"502","DOI":"10.1016\/j.ijpharm.2017.08.027","article-title":"Development of orodispersible minitablets with lorazepam using Gamlen Tablet Press","volume":"536","author":"Sznitowska","year":"2018","journal-title":"Int. J. Pharm."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Wasilewska, K., Ciosek-Skibi\u0144ska, P., Lenik, J., Sr\u010di\u010d, S., Basa, A., and Winnicka, K. (2020). Utilization of ethylcellulose microparticles with rupatadine fumarate in designing orodispersible minitablets with taste masking effect. Materials, 13.","DOI":"10.3390\/ma13122715"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"3","DOI":"10.4103\/2231-4040.93556","article-title":"Electronic tongue: An analytical gustatory tool","volume":"3","author":"Latha","year":"2012","journal-title":"J. Adv. Pharm. Technol. Res."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"751","DOI":"10.1016\/j.lwt.2015.03.019","article-title":"Masking of bitterness in dairy protein hydrolysates: Comparison of an electronic tongue and a trained sensory panel as means of directing the masking strategy","volume":"63","author":"Newman","year":"2015","journal-title":"LWT\u2014Food Sci. Technol."},{"key":"ref_16","unstructured":"Electronic Medicines Compendium (2022, August 22). Tegretol 100 mg Tablets\u2014Summary of Product Characteristics (SmPC). Available online: https:\/\/www.medicines.org.uk\/emc\/product\/1040\/smpc."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"729","DOI":"10.1007\/s13318-016-0397-3","article-title":"Pharmacokinetics and pharmacogenetics of carbamazepine in children","volume":"42","author":"Djordjevic","year":"2017","journal-title":"Eur. J. Drug Metab. Pharm."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1016\/j.seizure.2020.10.018","article-title":"Current role of carbamazepine and oxcarbazepine in the management of epilepsy","volume":"83","author":"Beydoun","year":"2020","journal-title":"Seizure"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1111\/bcp.13400","article-title":"Pharmacokinetic interactions and dosing rationale for antiepileptic drugs in adults and children","volume":"84","author":"Danhof","year":"2018","journal-title":"Br. J. Clin. Pharmacol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"120854","DOI":"10.1016\/j.ijpharm.2021.120854","article-title":"A micro-extrusion 3D printing platform for fabrication of orodispersible printlets for pediatric use","volume":"605","year":"2021","journal-title":"Int. J. Pharm."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Panraksa, P., Zhang, B., Rachtanapun, P., Jantanasakulwong, K., Qi, S., and Jantrawut, P. (2022). \u2018Tablet-in-syringe\u2019: A novel dosing mechanism for dysphagic patients containing fast-disintegrating tablets fabricated using semisolid extrusion 3D printing. Pharmaceutics, 14.","DOI":"10.3390\/pharmaceutics14020443"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1498","DOI":"10.1093\/jpp\/rgab121","article-title":"Semi-solid extrusion 3D printing of starch-based soft dosage forms for the treatment of paediatric latent tuberculosis infection","volume":"74","author":"Chatzitaki","year":"2022","journal-title":"J. Pharm. Pharmacol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"771","DOI":"10.1208\/s12248-014-9598-3","article-title":"Understanding Pharmaceutical Quality by Design","volume":"16","author":"Yu","year":"2014","journal-title":"AAPS J."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Kayaroganam, P. (2021). Central composite design for response surface methodology and its application in pharmacy. Response Surface Methodology in Engineering Science, IntechOpen.","DOI":"10.5772\/intechopen.90965"},{"key":"ref_25","unstructured":"JMP (2022, August 22). The Prediction Profiler. Available online: https:\/\/www.jmp.com\/support\/help\/en\/16.2\/index.shtml#page\/jmp\/the-prediction-profiler.shtml."},{"key":"ref_26","unstructured":"British Pharmacopoeia Commission (2020). British Pharmacopoeia 2021, The Stationery Office on behalf of the MHRA."},{"key":"ref_27","unstructured":"United States Pharmacopoeial Convention (2019). The United States Pharmacopoeia: The National Formulary, United States Pharmacopoeial Convention."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1016\/j.ejpb.2017.01.022","article-title":"A minitablet formulation made from electrospun nanofibers","volume":"114","author":"Poller","year":"2017","journal-title":"Eur. J. Pharm. Biopharm."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/S0378-5173(97)04910-7","article-title":"Bioequivalence study of carbamazepine tablets: In vitro\/in vivo correlation","volume":"152","author":"Jung","year":"1997","journal-title":"Int. J. Pharm."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Abdelhakim, H.E., Coupe, A., Tuleu, C., Edirisinghe, M., and Craig, D.Q. (2021). Utilising co-axial electrospinning as a taste-masking technology for paediatric drug delivery. Pharmaceutics, 13.","DOI":"10.3390\/pharmaceutics13101665"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"2557","DOI":"10.1021\/acs.molpharmaceut.9b00159","article-title":"Electrospinning optimization of Eudragit E PO with and without chlorpheniramine maleate using a design of experiment approach","volume":"16","author":"Abdelhakim","year":"2019","journal-title":"Mol. Pharm."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"977","DOI":"10.1016\/j.xphs.2018.10.001","article-title":"Exploration and preparation of a dose-flexible regulation system for levetiracetam tablets via novel semi-solid extrusion three-dimensional printing","volume":"108","author":"Cui","year":"2019","journal-title":"J. Pharm. Sci."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1016\/j.jconrel.2021.02.027","article-title":"Semi-solid extrusion 3D printing in drug delivery and biomedicine: Personalised solutions for healthcare challenges","volume":"332","author":"Januskaite","year":"2021","journal-title":"J. Control. Release"},{"key":"ref_34","first-page":"270","article-title":"Orodispersible tablets: A comprehensive review","volume":"2","author":"Arora","year":"2013","journal-title":"Int. J. Res. Dev. Pharm. Life Sci."},{"key":"ref_35","unstructured":"British National Formulary for Children (2022, August 22). Carbamazepine. Available online: https:\/\/bnfc.nice.org.uk\/drugs\/carbamazepine\/."},{"key":"ref_36","first-page":"100133","article-title":"Integrating Pressure Sensor Control into Semi-Solid Extrusion 3D Printing to Optimize Medicine Manufacturing","volume":"4","author":"Ong","year":"2022","journal-title":"Int. J. Pharm."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"679","DOI":"10.3109\/03639045.2011.621433","article-title":"Discriminatory dissolution method for quality control measurements of carbamazepine immediate release tablets based on in vitro\u2013in vivo investigations","volume":"38","author":"Xu","year":"2012","journal-title":"Drug Dev. Ind. Pharm."},{"key":"ref_38","unstructured":"Thermo Fisher Scientific (2022, August 22). FTIR Basic Organic Functional Group Reference Chart. Available online: http:\/\/www.thermoscientific.com\/content\/dam\/tfs\/ATG\/CAD\/CAD%20Documents\/Application%20%26%20Technical%20Notes\/Molecular%20Spectroscopy\/FTIR\/FTIR%20Spectrometers\/XX51346-E-0215M-OrganicFunctionalChart.pdf."},{"key":"ref_39","unstructured":"Cullity, B.D., and Stock, S.R. (2001). Elements of X-ray Diffraction, Prentice Hall. [3rd ed.]."},{"key":"ref_40","unstructured":"Speakman, S.A. (2013). Introduction to X-ray Powder Diffraction Data Analysis. [Ph.D. Thesis, Center for Materials Science and Engineering at MIT]."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"120715","DOI":"10.1016\/j.ijpharm.2021.120715","article-title":"Stability of \u03b1-lactose monohydrate: The discovery of dehydration triggered solid-state epimerization","volume":"604","author":"Alzoubi","year":"2021","journal-title":"Int. J. Pharm."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"24807","DOI":"10.1039\/D1RA03960A","article-title":"Intermolecular interactions between \u03b2-cyclodextrin and water","volume":"11","author":"Guo","year":"2021","journal-title":"RSC Adv."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Tawfik, E.A., Scarpa, M., Abdelhakim, H.E., Bukhary, H.A., Craig, D.Q.M., Barker, S.A., and Orlu, M. (2021). A potential alternative orodispersible formulation to prednisolone sodium phosphate orally disintegrating tablets. Pharmaceutics, 13.","DOI":"10.3390\/pharmaceutics13010120"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"3411","DOI":"10.3390\/s100403411","article-title":"Advanced taste sensors based on artificial lipids with global selectivity to basic taste qualities and high correlation to sensory scores","volume":"10","author":"Kobayashi","year":"2010","journal-title":"Sensors"},{"key":"ref_45","unstructured":"National Center for Biotechnology Information (2022, August 22). PubChem Compound Summary for CID 2554, Carbamazepine, Available online: https:\/\/pubchem.ncbi.nlm.nih.gov\/compound\/2554."}],"container-title":["Pharmaceutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4923\/15\/1\/250\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T18:03:09Z","timestamp":1760119389000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4923\/15\/1\/250"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,1,11]]},"references-count":45,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2023,1]]}},"alternative-id":["pharmaceutics15010250"],"URL":"https:\/\/doi.org\/10.3390\/pharmaceutics15010250","relation":{},"ISSN":["1999-4923"],"issn-type":[{"value":"1999-4923","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,1,11]]}}}