{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T11:48:14Z","timestamp":1790596094170,"version":"4.1.0"},"reference-count":50,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T00:00:00Z","timestamp":1759968000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000038","name":"United States Food and Drug Administration","doi-asserted-by":"publisher","award":["1U01FD006487-01"],"award-info":[{"award-number":["1U01FD006487-01"]}],"id":[{"id":"10.13039\/100000038","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000001","name":"National Science Foundation","doi-asserted-by":"publisher","award":["2140452-CMMI-EPSRC"],"award-info":[{"award-number":["2140452-CMMI-EPSRC"]}],"id":[{"id":"10.13039\/100000001","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Background\/Objectives: Glidants and lubricants are commonly used pharmaceutical excipients that enhance powder flowability and reduce inter-particle friction, respectively, but they also negatively impact critical quality attributes such as tablet tensile strength and drug release rate. Quantifying these effects is essential as the pharmaceutical industry transitions from batch to continuous manufacturing. Methods: This study develops a rational-function-based modeling approach to capture the effects of lubricants and glidants on tableting. The framework automatically identifies upstream critical material attributes and process parameters, such as excipient concentration and mixing time, and describes their coupling to first and second orders. Reduced-order models were constructed to evaluate the influence of these variables on the four stages of powder compaction\u2014die filling, compaction, unloading, and ejection\u2014using formulations composed of 10% acetaminophen, microcrystalline cellulose, and varying small concentrations of magnesium stearate or colloidal silica. Tablets were fabricated across a wide range of relative densities by varying dosing position and turret speed. Results: The modeling approach successfully quantified the effects of lubricant and glidant mixing conditions on each compaction stage, providing mechanistic insight into how upstream conditions propagate through the tableting process and influence critical quality attributes. Conclusions: Overall, the rational-function-based framework offers a systematic approach to quantify and predict the impact of lubricants and glidants on tablet performance, thereby enhancing product and process understanding in continuous manufacturing.<\/jats:p>","DOI":"10.3390\/ph18101514","type":"journal-article","created":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T16:54:31Z","timestamp":1760028871000},"page":"1514","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Rational Function-Based Approach for Integrating Tableting Reduced-Order Models with Upstream Unit Operations: Lubricants and Glidants Case Study"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-9448-9758","authenticated-orcid":false,"given":"Sunidhi","family":"Bachawala","sequence":"first","affiliation":[{"name":"School of Mechanical Engineering, Purdue University, West Lafayette, IN 47907, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dominik Tomasz","family":"Nasilowski","sequence":"additional","affiliation":[{"name":"School of Mechanical Engineering, Purdue University, West Lafayette, IN 47907, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcial","family":"Gonzalez","sequence":"additional","affiliation":[{"name":"School of Mechanical Engineering, Purdue University, West Lafayette, IN 47907, USA"},{"name":"Ray W. Herrick Laboratories, Purdue University, West Lafayette, IN 47907, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1016\/j.ijpharm.2011.02.032","article-title":"Mixing order of glidant and lubricant\u2014Influence on powder and tablet properties","volume":"409","author":"Pingali","year":"2011","journal-title":"Int. J. Pharm."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1208\/pt0804089","article-title":"Lubrication potential of magnesium stearate studied on instrumented rotary tablet press","volume":"8","author":"Patel","year":"2007","journal-title":"Aaps PharmSciTech"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"627","DOI":"10.3109\/03639049209058556","article-title":"The Physics of Tablet Compaction Revisited","volume":"18","author":"Wray","year":"1992","journal-title":"Drug Dev. 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