{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,21]],"date-time":"2026-02-21T11:25:17Z","timestamp":1771673117901,"version":"3.50.1"},"reference-count":57,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2025,4,1]],"date-time":"2025-04-01T00:00:00Z","timestamp":1743465600000},"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>Objectives: We investigated the compression mechanisms for loxoprofen sodium (LXP), which is known to occur as a dihydrate, and identified parameters that influence the tablet hardness of LXP tablets prepared by the wet granulation method. Method: LXP granules were prepared with water or ethanol as the solvent, dried under various conditions and sieved for particle size control, with 1% Mg-st added before tablet compression. Results: The findings indicated that both the granulation solvent and drying temperature significantly impacted the tablet hardness. Granules prepared with ethanol exhibited higher hardness as compared with those prepared with water. The tablet hardness varied with varying drying temperatures. Discussion: Principal component analysis (PCA) identified positive correlations between the tablet hardness and the surface free energy (SFE), polar component (\u03b3(p)), and cohesion, and a negative correlation with the dispersive component (\u03b3(d)). Granules prepared with ethanol exhibited a higher \u03b3(p), likely due to the differing solubility in ethanol and water, leading to enhanced interparticle binding. This study confirmed that use of the eutectic mixture of LXP and Mg-st exerted no significant influence. Crystal structure analysis indicated that the hydration states varied according to the drying temperature, suggesting the higher \u03b3(p) in anhydrous forms, due to the lower hydrophobicity, contributed to increased tablet hardness. Conclusion: This research offers insights for optimizing the formulation conditions to improve the LXP tablet hardness. Appropriate selection of the solvent and drying temperature mitigates tablet hardness issues, while assessment of SFE can help in the selection of suitable additives.<\/jats:p>","DOI":"10.3390\/pharmaceutics17040455","type":"journal-article","created":{"date-parts":[[2025,4,1]],"date-time":"2025-04-01T08:21:41Z","timestamp":1743495701000},"page":"455","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Granulation Methods and the Mechanisms for Improving Hardness of Loxoprofen Sodium Hydrate-Containing Tablets"],"prefix":"10.3390","volume":"17","author":[{"given":"Aya","family":"Kuwata","sequence":"first","affiliation":[{"name":"Research & Development Headquarters Self-Medication, Taisho Pharmaceutical Co., Ltd., 1-403 Yoshino-Cho, Kita-ku, Saitama 331-9530, Japan"},{"name":"Department of Physical Chemistry, Hoshi University, 2-4-41 Ebara, Tokyo 142-0063, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Agata","family":"Ishikawa","sequence":"additional","affiliation":[{"name":"Research & Development Headquarters Self-Medication, Taisho Pharmaceutical Co., Ltd., 1-403 Yoshino-Cho, Kita-ku, Saitama 331-9530, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tetsuo","family":"Ono","sequence":"additional","affiliation":[{"name":"Research & Development Headquarters Self-Medication, Taisho Pharmaceutical Co., Ltd., 1-403 Yoshino-Cho, Kita-ku, Saitama 331-9530, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5255-5129","authenticated-orcid":false,"given":"Etsuo","family":"Yonemochi","sequence":"additional","affiliation":[{"name":"Department of Physical Chemistry, Hoshi University, 2-4-41 Ebara, Tokyo 142-0063, Japan"},{"name":"Department of Physical Chemistry, International University of Health and Welfare, 4-3 Kozunomori, Chiba 286-8686, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,4,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"771","DOI":"10.1007\/s40261-016-0440-9","article-title":"Loxoprofen: A Review in Pain and Inflammation","volume":"36","author":"Greig","year":"2016","journal-title":"Clin. 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