{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,22]],"date-time":"2026-08-22T04:27:52Z","timestamp":1787372872618,"version":"build-2736575974"},"reference-count":97,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T00:00:00Z","timestamp":1787184000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004504","name":"Research Council of Lithuania","doi-asserted-by":"publisher","award":["S-A-UEI-23-7"],"award-info":[{"award-number":["S-A-UEI-23-7"]}],"id":[{"id":"10.13039\/501100004504","id-type":"DOI","asserted-by":"publisher"}]},{"award":["S-A-UEI-23-7"],"award-info":[{"award-number":["S-A-UEI-23-7"]}],"id":[{"id":"https:\/\/ror.org\/02gs16m83","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Background: Three-dimensional printing (3DP) is rapidly advancing personalised medicine, yet systematic performance comparison with conventional manufacturing remains limited, particularly for plant-based formulations. Methods: This study compared tablets containing plant-based APIs (cannabidiol, apigenin, and luteolin) produced via conventional hot moulding and semi-solid extrusion (SSE) 3DP. The formulations were evaluated for physicochemical, mechanical, rheological, structural, and drug-release properties. Results: Both manufacturing methods produced tablets with comparable dimensions and mass; however, pronounced formulation-dependent differences were observed in mechanical strength, rheology, and microstructure. The molecular modelling predictions were consistent with the experimental findings. Agar\u2013pectin exhibited the strongest predicted polymer\u2013polymer and polymer\u2013API interactions, including multiple hydrogen bonds, and formed a comparatively dense and cohesive matrix associated with slower API release. In contrast, the weaker interactions predicted for gelatine\u2013pectin were associated with a less cohesive and more porous matrix that facilitated medium penetration, API diffusion, and drug release. SSE printlets generally exhibited greater porosity and more heterogeneous internal architectures than moulded tablets, resulting in enhanced drug release of approximately 95%. Micro-CT analysis provided important structural confirmation; API incorporation increased the void volume of gelatine\u2013pectin printlets from 1.15% to 8.77%, demonstrating that disruption of polymer interactions contributed to pore formation and enhanced molecular diffusion. The observed release behaviour correlated with predicted molecular interactions and experimentally observed microstructural features, where increased porosity and weaker polymer\u2013API interactions facilitated enhanced drug diffusion. Conclusions: Overall, SSE-3DP outperformed conventional moulding, demonstrating superior tunability and performance. This work provides a mechanistically informed strategy for designing plant-based, personalised natural products using 3DP technologies.<\/jats:p>","DOI":"10.3390\/pharmaceutics18081035","type":"journal-article","created":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T16:05:19Z","timestamp":1787241919000},"page":"1035","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Mechanistic Comparison of Semi-Solid Extrusion 3D-Printed Printlets and Hot-Moulded Tablets: Linking Polymer\u2013API Interactions, Microstructure, and Dissolution of Plant-Based Formulations"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4676-8026","authenticated-orcid":false,"given":"Emilija","family":"Nemickaite","sequence":"first","affiliation":[{"name":"Department of Drug Technology and Social Pharmacy, Faculty of Pharmacy, Medical Academy, Lithuanian University of Health Sciences, Sukileliu pr. 13, LT-50161 Kaunas, Lithuania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pooja","family":"Todke","sequence":"additional","affiliation":[{"name":"Department of Drug Technology and Social Pharmacy, Faculty of Pharmacy, Medical Academy, Lithuanian University of Health Sciences, Sukileliu pr. 13, LT-50161 Kaunas, Lithuania"},{"name":"Institute of Pharmaceutical Technologies, Faculty of Pharmacy, Medical Academy, Lithuanian University of Health Sciences, Sukileliu pr. 13, LT-50161 Kaunas, Lithuania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vaidotas","family":"Cicenas","sequence":"additional","affiliation":[{"name":"Ultrasound Research Institute, Kaunas University of Technology, K. Barsausko Str. 59, LT-51423 Kaunas, Lithuania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8073-5597","authenticated-orcid":false,"given":"Elena","family":"Jasi\u016bnien\u0117","sequence":"additional","affiliation":[{"name":"Ultrasound Research Institute, Kaunas University of Technology, K. Barsausko Str. 59, LT-51423 Kaunas, Lithuania"},{"name":"Department of Electronics Engineering, Kaunas University of Technology, Studentu Str. 50, LT-51368 Kaunas, Lithuania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mindaugas","family":"Marksa","sequence":"additional","affiliation":[{"name":"Department of Analytical and Toxicological Chemistry, Medical Academy, Lithuanian University of Health Sciences, LT-50161 Kaunas, Lithuania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1744-2932","authenticated-orcid":false,"given":"Jurga","family":"Bernatoniene","sequence":"additional","affiliation":[{"name":"Department of Drug Technology and Social Pharmacy, Faculty of Pharmacy, Medical Academy, Lithuanian University of Health Sciences, Sukileliu pr. 13, LT-50161 Kaunas, Lithuania"},{"name":"Institute of Pharmaceutical Technologies, Faculty of Pharmacy, Medical Academy, Lithuanian University of Health Sciences, Sukileliu pr. 13, LT-50161 Kaunas, Lithuania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,20]]},"reference":[{"key":"ref_1","unstructured":"Kawale, S.R., and Patel, M.R. 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