{
  "abstract": "The purpose of this study was to evaluate the precipitation profiles of dipyridamole (DPM) in a biorelevant pH-shift dissolution test under a clinically relevant dose-to-fluid volume (Dose/FV) ratio, focusing on liquid-liquid phase separation (LLPS). In the pH-shift dissolution test, DPM was added to an hydrochloric acid solution (pH 2.0, 450 mL) as the solid drug substance or formulation (Dose/FV = 400 µg/mL, corresponding to a 100 mg dose in 250 mL). In the pH-shift precipitation test, DPM was fully dissolved before the pH shift. After 10 min, the pH was adjusted to 6.5 by adding a 10-fold concentrated bicarbonate buffer (BCB), yielding the conditions of FV = 500 mL and BCB = 10 mM. Under pH 2.0, approximately 90% of the dose dissolved within 10 min. Immediately after the pH shift, turbidity appeared within 1 s and the dissolved DPM concentration dropped to the LLPS concentration (97 µg/mL) (STEP 1), remained there for 3-5 min, and then declined toward the crystalline solubility (6 µg/mL) (STEP 2). In the pH-shift precipitation test examined under polarized light microscopy, noncrystalline droplets appeared instantaneously and persisted for approximately 2 min before crystallization. These results indicate that STEP 1 and STEP 2 corresponded to LLPS and crystallization, respectively. Although DPM is a free-base drug that does not generate LLPS on its own and has been categorized as a rapid crystallizer, this study experimentally demonstrated a two-step precipitation profile under clinically relevant pH-shift and Dose/FV conditions, in which LLPS preceded crystallization.",
  "abstract_shown": true,
  "affiliations": [],
  "article_type": null,
  "arxiv": null,
  "author_total": 3,
  "authors": [
    {
      "name": "Hibiki Yamamoto"
    },
    {
      "name": "Ayame Ito"
    },
    {
      "name": "Kiyohiko Sugano"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/5den3svjdamny.bib",
  "cited_by": 0,
  "doi": "10.1248/cpb.c26-00371",
  "fulltext_url": "https://www.jstage.jst.go.jp/article/cpb/74/10/74_c26-00371/_article",
  "id": "5den3svjdamny",
  "issns": [
    "1347-5223",
    "0009-2363"
  ],
  "landing_url": "https://www.jstage.jst.go.jp/article/cpb/74/10/74_c26-00371/_article",
  "language": null,
  "licence": "CC-BY-NC",
  "licence_label": "CC BY-NC",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by-nc/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "jstage-journal",
      "chemistry/medicinal"
    ],
    [
      "openalex",
      "3003|Drug Solubulity and Delivery Systems"
    ]
  ],
  "openalex": "W7221109889",
  "pdf_url": "https://www.jstage.jst.go.jp/article/cpb/74/10/74_c26-00371/_pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-10",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/5den3svjdamny.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:34Z",
      "native_id": "10.1248/cpb.c26-00371",
      "source": "jstage",
      "url": "https://www.jstage.jst.go.jp/article/cpb/74/10/74_c26-00371/_article"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:3003|Drug Solubulity and Delivery Systems",
      "subfield": "pharmacology-toxicology"
    }
  ],
  "title": "Precipitation Profiles of Dipyridamole in Biorelevant pH-Shift Dissolution Test with Clinically Relevant Dose-to-Fluid Volume Ratio Focusing on Liquid–Liquid Phase Separation",
  "title_text": "Precipitation Profiles of Dipyridamole in Biorelevant pH-Shift Dissolution Test with Clinically Relevant Dose-to-Fluid Volume Ratio Focusing on Liquid–Liquid Phase Separation",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:17:34Z",
  "url": "https://research.draconitic.com/paper/5den3svjdamny",
  "venue": "Chemical and Pharmaceutical Bulletin",
  "versions": []
}