{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,30]],"date-time":"2026-05-30T01:16:49Z","timestamp":1780103809505,"version":"3.54.0"},"reference-count":26,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2023,8,1]],"date-time":"2023-08-01T00:00:00Z","timestamp":1690848000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Biopharm &amp; Drug Disp"],"published-print":{"date-parts":[[2023,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The present study was undertaken to develop a self\u2010micellizing solid dispersion (SMSD) of tacrolimus (TAC) to improve the biopharmaceutical properties of TAC. An SMSD formulation of TAC (SMSD\/TAC) and amorphous solid dispersion formulation of TAC (ASD\/TAC) were prepared with Soluplus<jats:sup>\u00ae<\/jats:sup>, an amphiphilic copolymer, and hydroxypropyl cellulose, respectively. Physicochemical properties were characterized in terms of morphology, crystallinity, storage stability, interaction of TAC with Soluplus<jats:sup>\u00ae<\/jats:sup>, and micelle\u2010forming potency; pharmacokinetic behavior was also evaluated in rats. Tacrolimus in both formulations was in an amorphous state. After storage at 40\u00b0C\/75% relativity humidity for 4\u00a0weeks, there were no significant changes in the crystallinity of TAC between nonaged and aged SMSD\/TAC, whereas slight recrystallization was observed in aged ASD\/TAC. The results of circular dichroism (CD) and infrared spectroscopic analyses were indicative of the potent drug\u2013polymer interaction in SMSD\/TAC, possibly leading to the prevention of recrystallization. Compared with other TAC samples, SMSD\/TAC exhibited significant improvement in the dissolution behavior of TAC through the immediate formation of fine micelles. After the oral administration of TAC samples (10\u00a0mg TAC\/kg) to rats, there was marked enhancement in systemic exposure to TAC with both formulations; in particular, SMSD\/TAC achieved an increase in bioavailability ca. 20\u2010fold higher than crystalline TAC. The SMSD approach might provide an effective dosage form for TAC with enhanced physicochemical stability and oral absorption.<\/jats:p>","DOI":"10.1002\/bdd.2373","type":"journal-article","created":{"date-parts":[[2023,8,1]],"date-time":"2023-08-01T13:23:39Z","timestamp":1690896219000},"page":"387-395","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Self\u2010micellizing solid dispersion of tacrolimus: Physicochemical and pharmacokinetic characterization"],"prefix":"10.1002","volume":"44","author":[{"given":"Keisuke","family":"Makino","sequence":"first","affiliation":[{"name":"Laboratory of Biopharmacy School of Pharmaceutical Sciences University of Shizuoka  Shizuoka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryota","family":"Tsukada","sequence":"additional","affiliation":[{"name":"Laboratory of Biopharmacy School of Pharmaceutical Sciences University of Shizuoka  Shizuoka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atsushi","family":"Kambayashi","sequence":"additional","affiliation":[{"name":"Laboratory of Biopharmacy School of Pharmaceutical Sciences University of Shizuoka  Shizuoka Japan"},{"name":"Pharmaceutical Research and Technology Labs Astellas Pharma Inc.  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