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Contrasting with reported crystalline precipitates of weakly basic drugs, this study investigates XZP8257 (C\n                    <jats:sub>27<\/jats:sub>\n                    H\n                    <jats:sub>23<\/jats:sub>\n                    Cl\n                    <jats:sub>2<\/jats:sub>\n                    N\n                    <jats:sub>3<\/jats:sub>\n                    O\n                    <jats:sub>4<\/jats:sub>\n                    S), a poorly soluble weakly acidic\/zwitterionic compound (BCS II), to explore how GI fluid composition governs precipitate formation and its resulting physicochemical properties. Precipitates were generated in simulated intestinal media with varied bile salt concentrations and pH values. Their solid\u2010state forms were characterized using XRD, SEM, FTIR, and DSC, whereas dissolution performance was evaluated via equilibrium solubility and intrinsic dissolution rate (IDR) measurements. Elevated bile salt concentrations induced a molecular structural transition in XZP8257 and facilitated the formation of crystalline\u2013amorphous mixed precipitates, a phenomenon distinct from the crystalline precipitates typically reported. These novel precipitates exhibited a 5.29\u2010 to 22.1\u2010fold increase in equilibrium solubility and a 0.7\u2010 to 2.35\u2010fold improvement in IDR compared to the crystalline API. This study reveals that for weakly acidic compounds like XZP8257, precipitate formation in the GI tract can lead to high energy, readily redissolving solid forms, potentially enhancing rather than limiting absorption. This challenges the uniform negative view of precipitation and underscores the necessity of compound\u2010specific precipitate characterization to accurately predict oral absorption, especially in physiologically based biopharmaceutics models.\n                  <\/jats:p>","DOI":"10.1002\/bdd.70025","type":"journal-article","created":{"date-parts":[[2026,4,7]],"date-time":"2026-04-07T10:46:59Z","timestamp":1775558819000},"page":"88-99","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Improvement of XZP8257 Dissolution Properties Through Amorphous and Mixed\u2010Phase Precipitate Formation in Biorelevant Media"],"prefix":"10.1002","volume":"47","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6132-133X","authenticated-orcid":false,"given":"Miao","family":"Zhang","sequence":"first","affiliation":[{"name":"Drug Clinical Trial Center Peking University Third Hospital  Beijing China"},{"name":"Department of Pharmaceutical Sciences, School of Pharmacy, Bouve College of Health Sciences Northeastern University  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shudong","family":"Zhang","sequence":"additional","affiliation":[{"name":"NMPA Key Laboratory for Research and Evaluation of Generic Drugs Beijing Institute for Drug Control  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bin","family":"Wu","sequence":"additional","affiliation":[{"name":"NMPA Key Laboratory for Research and Evaluation of Generic Drugs Beijing Institute for Drug Control  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhe","family":"Zhang","sequence":"additional","affiliation":[{"name":"NMPA Key Laboratory for Research and Evaluation of Generic Drugs Beijing Institute for Drug Control  Beijing 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