{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T15:16:23Z","timestamp":1776352583041,"version":"3.51.2"},"reference-count":42,"publisher":"MDPI AG","issue":"20","license":[{"start":{"date-parts":[[2022,10,20]],"date-time":"2022-10-20T00:00:00Z","timestamp":1666224000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Applied Sciences"],"abstract":"<jats:p>Individualised medicine demands the formulation of pharmacotherapy in accordance with the characteristics of each patient\u2019s health condition, and paediatrics is one of the areas that needs this approach. The 3D printing of oral doses is one method for achieving customised medicine in paediatrics. In this work, pre-formulation studies were conducted to evaluate the viability of using specific raw materials to produce 3D printed dosage forms based on two active pharmaceutical ingredients (APIs), ondansetron and esomeprazole, which are important for therapeutic customisation in paediatrics. Pre-formulation studies were carried out by characterising the physical and chemical properties of selected raw materials, selected APIs and their mixtures, using analytical methods such as scanning electron microscopy (SEM), X-ray powder diffraction (X-RPD), simultaneous thermal analysis (STA) and differential scanning calorimetry (DSC). The flowability of powders, compatibility and stability studies were also performed. Among all the ingredients selected, the PVPs (K17, K25 and K90) had the best characteristics to incorporate both forms of Esomeprazole Mg in a formulation to produce extrudates. The results obtained validated the use of some selected raw materials for tablet manufacture by the 3D printing approach.<\/jats:p>","DOI":"10.3390\/app122010585","type":"journal-article","created":{"date-parts":[[2022,10,20]],"date-time":"2022-10-20T20:35:55Z","timestamp":1666298155000},"page":"10585","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Personalised Esomeprazole and Ondansetron 3D Printing Formulations in Hospital Paediatric Environment: I-Pre-Formulation Studies"],"prefix":"10.3390","volume":"12","author":[{"given":"Mariana","family":"Ferreira","sequence":"first","affiliation":[{"name":"Instituto de Investiga\u00e7\u00e3o, Inova\u00e7\u00e3o e Desenvolvimento (FP-I3ID), Biomedical and Health Sciences Research Unit (FP-BHS), Faculdade de Ci\u00eancias da Sa\u00fade, Universidade Fernando Pessoa, Rua Carlos da Maia 296, 4200-150 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5080-032X","authenticated-orcid":false,"given":"Carla M.","family":"Lopes","sequence":"additional","affiliation":[{"name":"Instituto de Investiga\u00e7\u00e3o, Inova\u00e7\u00e3o e Desenvolvimento (FP-I3ID), Biomedical and Health Sciences Research Unit (FP-BHS), Faculdade de Ci\u00eancias da Sa\u00fade, Universidade Fernando Pessoa, Rua Carlos da Maia 296, 4200-150 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1357-1764","authenticated-orcid":false,"given":"Hugo","family":"Gon\u00e7alves","sequence":"additional","affiliation":[{"name":"Paralab, SA, Rua Dr. Joaquim Manuel Costa 946 B, 4420-437 Valbom, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6499-310X","authenticated-orcid":false,"given":"Jo\u00e3o F.","family":"Pinto","sequence":"additional","affiliation":[{"name":"iMed-Research Institute for Medicines, Faculdade de Farm\u00e1cia, Universidade de Lisboa, Av. Prof. Gama Pinto, 1640-003 Lisboa, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7270-5702","authenticated-orcid":false,"given":"Jos\u00e9","family":"Catita","sequence":"additional","affiliation":[{"name":"Instituto de Investiga\u00e7\u00e3o, Inova\u00e7\u00e3o e Desenvolvimento (FP-I3ID), Biomedical and Health Sciences Research Unit (FP-BHS), Faculdade de Ci\u00eancias da Sa\u00fade, Universidade Fernando Pessoa, Rua Carlos da Maia 296, 4200-150 Porto, Portugal"},{"name":"Paralab, SA, Rua Dr. Joaquim Manuel Costa 946 B, 4420-437 Valbom, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2022,10,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1472","DOI":"10.1093\/ajhp\/zxz161","article-title":"Pharmacokinetic considerations in pediatric pharmacotherapy","volume":"76","author":"Lim","year":"2019","journal-title":"Am. J. Health-Syst. Pharm."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1080","DOI":"10.1001\/archpediatrics.2009.229","article-title":"Safety and transparency of pediatric drug trials","volume":"163","author":"Benjamin","year":"2009","journal-title":"Arch. Pediatr. Adolesc. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"53","DOI":"10.3390\/pharmaceutics3010053","article-title":"Factors and Mechanisms for Pharmacokinetic Differences between Pediatric Population and Adults","volume":"3","author":"Fernandez","year":"2011","journal-title":"Pharmaceutics"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"777","DOI":"10.1111\/bcp.13160","article-title":"Scaling clearance in paediatric pharmacokinetics: All models are wrong, which are useful?","volume":"83","author":"Germovsek","year":"2017","journal-title":"Br. J. Clin. Pharm."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1153","DOI":"10.1007\/s00467-019-04304-9","article-title":"Pharmacokinetics in children with chronic kidney disease","volume":"35","author":"Schijvens","year":"2020","journal-title":"Pediatr. Nephrol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1310\/hpj5202-124","article-title":"Pharmacists and Pediatric Medication Adherence: Bridging the Gap","volume":"52","author":"LaRochelle","year":"2017","journal-title":"Hosp. Pharm."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"4349","DOI":"10.1111\/bcp.15293","article-title":"From paediatric formulations development to access: Advances made and remaining challenges","volume":"88","author":"Litalien","year":"2022","journal-title":"Br. J. Clin. Pharmacol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1136\/ejhpharm-2016-001034","article-title":"Compatibility of proton pump inhibitors in a preservative-free suspending vehicle","volume":"25","author":"Polonini","year":"2018","journal-title":"Eur. J. Hosp. Pharm."},{"key":"ref_9","unstructured":"Pratt, V.M., Scott, S.A., Pirmohamed, M., Esquivel, B., Kane, M.S., Kattman, B.L., and Malheiro, A.J. (2012). Esomeprazole Therapy and CYP2C19 Genotype. Medical Genetics Summaries, National Center for Biotechnology Information (US)."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"441","DOI":"10.2165\/00003088-200544050-00001","article-title":"Pharmacokinetics of proton pump inhibitors in children","volume":"44","author":"Litalien","year":"2005","journal-title":"Clin. Pharm."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Kader, R., Liminga, G., Ljungman, G., and Paulsson, M. (2021). Manipulations of Oral Medications in Paediatric Neurology and Oncology Care at a Swedish University Hospital: Health Professionals\u2019 Attitudes and Sources of Information. Pharmaceutics, 13.","DOI":"10.3390\/pharmaceutics13101676"},{"key":"ref_12","unstructured":"Griddine, A., and Bush, J.S. (2022). Ondansetron, StatPearls Publishing."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1945","DOI":"10.1007\/s12272-011-1115-y","article-title":"Formulation and in vivo evaluation of ondansetron orally disintegrating tablets using different superdisintegrants","volume":"34","author":"Sheshala","year":"2011","journal-title":"Arch. Pharmacal Res."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Allahham, N., Fina, F., Marcuta, C., Kraschew, L., Mohr, W., Gaisford, S., Basit, A.W., and Goyanes, A. (2020). Selective Laser Sintering 3D Printing of Orally Disintegrating Printlets Containing Ondansetron. Pharmaceutics, 12.","DOI":"10.3390\/pharmaceutics12020110"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1097\/ALN.0b013e31817fd8c8","article-title":"Droperidol and ondansetron-induced QT interval prolongation: A clinical drug interaction study","volume":"109","author":"Charbit","year":"2008","journal-title":"Anesthesiology"},{"key":"ref_16","first-page":"27","article-title":"Clinical utility of esomeprazole for treatment of gastroesophageal reflux disease in pediatric and adolescent patients","volume":"3","author":"Cardile","year":"2012","journal-title":"Adolesc. Health Med."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Silva, M.R.M.d., Dysars, L.P., dos Santos, E.P., and Ricci J\u00fanior, E. (2020). Preparation of extemporaneous oral liquid in the hospital pharmacy. Braz. J. Pharm. Sci., 56.","DOI":"10.1590\/s2175-97902019000418358"},{"key":"ref_18","first-page":"9","article-title":"Unitariza\u00e7\u00e3o De Doses Em Farm\u00e1cia Hospitalar","volume":"24","author":"Martins","year":"2012","journal-title":"Infarma"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/j.ijpharm.2004.12.013","article-title":"Accelerated aging: Prediction of chemical stability of pharmaceuticals","volume":"293","author":"Waterman","year":"2005","journal-title":"Int. J. Pharm."},{"key":"ref_20","first-page":"23","article-title":"Patient safety\u2014The role of human factors and systems engineering","volume":"153","author":"Carayon","year":"2010","journal-title":"Stud. Health Technol. Inform."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1080\/17425247.2017.1371698","article-title":"3D printing of oral drugs: A new reality or hype?","volume":"15","author":"Hsiao","year":"2018","journal-title":"Expert Opin. Drug Deliv."},{"key":"ref_22","first-page":"1","article-title":"Comparison of Different Types of 3D Printing Technologies","volume":"8","author":"Shiwpursad","year":"2018","journal-title":"Int. J. Sci. Res."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Varghese, R., Sood, P., Salvi, S., Karsiya, J., and Kumar, D. (2022). 3D printing in the pharmaceutical sector: Advances and evidences. Sens. Int., 3.","DOI":"10.1016\/j.sintl.2022.100177"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1007\/s40005-022-00561-3","article-title":"Three-Dimensional Printing for Oral Pharmaceutical Dosage Forms","volume":"52","author":"Kim","year":"2022","journal-title":"J. Pharm. Investig."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"856","DOI":"10.1016\/j.proeng.2015.12.570","article-title":"Dimensional and Surface Texture Characterization in Fused Deposition Modelling (FDM) with ABS plus","volume":"132","author":"Rivas","year":"2015","journal-title":"Procedia Eng."},{"key":"ref_26","first-page":"2313","article-title":"A review on pharmaceutical preformulation studies in formulation and development of new drug molecules","volume":"7","author":"Chaurasia","year":"2016","journal-title":"Int. J. Pharm. Sci. Res."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Deruyver, L., Rigaut, C., Lambert, P., Haut, B., and Goole, J. (2021). The importance of pre-formulation studies and of 3D-printed nasal casts in the success of a pharmaceutical product intended for nose-to-brain delivery. Adv. Drug Deliv. Rev., 175.","DOI":"10.1016\/j.addr.2021.113826"},{"key":"ref_28","unstructured":"Nogueira Prista, L., Correia Alves, A., Morgado, R., and Sousa Lobo, J. (2003). Tecnologia Farmac\u00eautica, Funda\u00e7\u00e3o Calouste Gulbenkian. [6th ed.]."},{"key":"ref_29","first-page":"25","article-title":"Understand the Effects of Moisture on Powder Behavior","volume":"110","author":"Armstrong","year":"2014","journal-title":"Chem. Eng. Prog."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/j.ijpharm.2007.06.017","article-title":"Mechanism of moisture induced variations in true density and compaction properties of microcrystalline cellulose","volume":"346","author":"Sun","year":"2008","journal-title":"Int. J. Pharm."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1098","DOI":"10.1208\/s12249-013-9994-5","article-title":"Note on the measurement of bulk density and tapped density of powders according to the European Pharmacopeia","volume":"14","author":"Splendor","year":"2013","journal-title":"AAPS PharmSciTech"},{"key":"ref_32","first-page":"7","article-title":"Friction conditions in a mass of metal powder","volume":"3","author":"Hausner","year":"1967","journal-title":"Int. J. Powder Met."},{"key":"ref_33","first-page":"163","article-title":"Evaluating flow properties of solids","volume":"72","author":"Carr","year":"1965","journal-title":"Chem. Eng."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Browne, E., Worku, Z.A., and Healy, A.M. (2020). Physicochemical Properties of Poly-Vinyl Polymers and Their Influence on Ketoprofen Amorphous Solid Dispersion Performance: A Polymer Selection Case Study. Pharmaceutics, 12.","DOI":"10.3390\/pharmaceutics12050433"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Skieneh, J., Khalili Najafabadi, B., Horne, S., and Rohani, S. (2016). Crystallization of Esomeprazole Magnesium Water\/Butanol Solvate. Molecules, 21.","DOI":"10.3390\/molecules21040544"},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Mizoguchi, R., and Uekusa, H. (2019). Elucidation of the Crystal Structures and Dehydration Behaviors of Ondansetron Salts. Crystals, 9.","DOI":"10.3390\/cryst9030180"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1023\/A:1007516718048","article-title":"What is the true solubility advantage for amorphous pharmaceuticals?","volume":"17","author":"Hancock","year":"2000","journal-title":"Pharm. Res."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1007\/s13346-015-0221-7","article-title":"Preparation and characterization of pH-sensitive methyl methacrylate-g-starch\/hydroxypropylated starch hydrogels: In vitro and in vivo study on release of esomeprazole magnesium","volume":"5","author":"Kumar","year":"2015","journal-title":"Drug Deliv. Transl. Res."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1007\/s12247-019-09373-9","article-title":"RSM-Based Design and Optimization of Transdermal Film of Ondansetron HCl","volume":"15","author":"Parhi","year":"2020","journal-title":"J. Pharm. Innov."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Azubuike, C.P., and Okhamafe, A.O. (2012). Physicochemical, spectroscopic and thermal properties of microcrystalline cellulose derived from corn cobs. Int. J. Recycl. Org. Waste Agric., 1.","DOI":"10.1186\/2251-7715-1-9"},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Voronova, M., Rubleva, N., Kochkina, N., Afineevskii, A., Zakharov, A., and Surov, O. (2018). Preparation and Characterization of Polyvinylpyrrolidone\/Cellulose Nanocrystals Composites. Nanomaterials, 8.","DOI":"10.3390\/nano8121011"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1016\/j.jpba.2011.05.017","article-title":"Compatibility study between ketoprofen and pharmaceutical excipients used in solid dosage forms","volume":"56","author":"Bandur","year":"2011","journal-title":"J. Pharm. Biomed. Anal."}],"container-title":["Applied Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-3417\/12\/20\/10585\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T00:57:58Z","timestamp":1760144278000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-3417\/12\/20\/10585"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,10,20]]},"references-count":42,"journal-issue":{"issue":"20","published-online":{"date-parts":[[2022,10]]}},"alternative-id":["app122010585"],"URL":"https:\/\/doi.org\/10.3390\/app122010585","relation":{},"ISSN":["2076-3417"],"issn-type":[{"value":"2076-3417","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,10,20]]}}}