{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T06:05:17Z","timestamp":1771481117259,"version":"3.50.1"},"reference-count":36,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2026,2,4]],"date-time":"2026-02-04T00:00:00Z","timestamp":1770163200000},"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>Background\/Objectives: Manual preparation of semisolid formulations (creams, ointments, gels) is prone to variability in mixing energy and time, which may compromise uniform API distribution. This study aimed to evaluate an Electronic Mortar and Pestle (EMP; Unguator\u2122) as a standardized compounding tool, with objectives to: (i) validate stability-indicating UHPLC methods; (ii) assess content uniformity across jar strata; (iii) quantify the impact of mixing time and rotation speed via design of experiments (DOE); and (iv) verify cleaning effectiveness and cross-contamination risk. Methods: Five representative formulations were compounded: urea 40%, clobetasol 0.05%, diclofenac 2.5% in hyaluronic acid 3% gel, urea 10% + salicylic acid 1%, and hydroquinone 5%. UHPLC methods were validated per ICH Q2(R2) and stress-tested under acid, base, oxidative, thermal, and UV conditions. Homogeneity was assessed by stratified sampling (top\/middle\/bottom). A 32 factorial DOE (time: 2\/6\/10 min; speed: 600\/1500\/2400 rpm) modeled effects on % label claim and RSD. Cleaning validation employed hydroquinone as a tracer, with swab sampling pre-\/post-use and post-sanitization analyzed by HPLC. Results: All UHPLC methods met specificity, linearity, precision, accuracy, and sensitivity criteria and were stability-indicating (Rs \u2265 1.5). Formulations achieved 90\u2013110% label claim with strata CV \u2264 5%. DOE revealed speed as the dominant factor for clobetasol, urea, and diclofenac, while time was more influential for salicylic acid; gels exhibited curvature, indicating diminishing returns at high rpm. Model-predicted optima were implementable on the Unguator\u2122 with minor rounding of rpm\/time. Cleaning validation confirmed post-sanitization residues below LOQ and &lt;10 ppm acceptance. Conclusions: The Unguator\u2122 provides a practical, parameter-controlled route for compounding pharmacies to standardize semisolid preparations, achieving reproducible layer-to-layer content uniformity within predefined criteria under the evaluated conditions through programmable set-points and validated cycles. DOE-derived rpm\u2013time relationships define an operational design space within the studied ranges and support selection of implementable device settings and set-points. Importantly, the DOE-derived \u201coptima\u201d in this study are optimized for assay-based content uniformity (mean % label claim and strata variability). Cleaning validation supports a closed, low-cross-contamination workflow, facilitating consistent routines for both routine and complex formulations. Overall, the work implements selected QbD elements (QTPP\u2014Quality Target Product Profile; CQA\u2014Critical Quality Attribute definition; CPP\u2014Critical Process Parameter identification; operational design space; and a proposed control strategy) and should be viewed as a step toward broader lifecycle QbD implementation in compounding.<\/jats:p>","DOI":"10.3390\/pharmaceutics18020205","type":"journal-article","created":{"date-parts":[[2026,2,4]],"date-time":"2026-02-04T17:20:14Z","timestamp":1770225614000},"page":"205","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Quality-by-Design Compounding of Semisolids Using an Electronic Mortar and Pestle Device for Compounding Pharmacies: Uniformity, Stability, and Cleaning"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2119-3660","authenticated-orcid":false,"given":"Hudson","family":"Polonini","sequence":"first","affiliation":[{"name":"Fagron, Fascinatio Boulevard, 350, 3065 WB Rotterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carolina","family":"Schettino Kegele","sequence":"additional","affiliation":[{"name":"Fagron, Fascinatio Boulevard, 350, 3065 WB Rotterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-7226-7334","authenticated-orcid":false,"given":"Savvas","family":"Koulouridas","sequence":"additional","affiliation":[{"name":"Fagron, Fascinatio Boulevard, 350, 3065 WB Rotterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6026-9608","authenticated-orcid":false,"given":"Marcone","family":"Augusto Leal de Oliveira","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Federal University of Juiz de Fora, Juiz de Fora 36036-900, MG, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1016\/j.jaad.2019.10.038","article-title":"A Review of the Clinical Indications, General Principles and Techniques Related to Compounding","volume":"83","author":"Campbell","year":"2020","journal-title":"J. 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