{
  "abstract": "The pressure–temperature behavior of anhydrous caffeine’s two polymorphs—form II (monoclinic) and form I (trigonal)—was characterized by high–resolution powder diffraction, electron microscopy, differential scanning calorimetry and high–pressure thermal analysis. Measured transition enthalpies are 19 J g⁻1 for the solid–solid conversion and 109 J g⁻1 for melting of form I. Direct application of the Clapeyron equation to these state functions yields linear equilibrium relations with slopes of dP/dT =4.15 MPa K⁻1 for the I-II equilibrium and 2.6 MPa K⁻1 for the I–L equilibrium, values that match the direct measurements at different pressures and temperatures in this study and in the literature. The resulting phase diagram shows divergent I-II and I–L lines with increasing pressure, placing caffeine in Bakhuis-Roozeboom’s case 2 (overall enantiotropy) and locating the I–II–L triple point at negative pressure, thus metastable. Form I consistently has a larger specific volume than form II, and the volume change on melting follows the typical VL/VS ratio of about 1.11 for organic solids. The close agreement between experiment and Clapeyron–based (topological) predictions demonstrates that the topological method correctly captures polymorphic stability across broad pressure and temperature ranges.",
  "abstract_shown": true,
  "affiliations": [],
  "article_type": null,
  "arxiv": null,
  "author_total": 6,
  "authors": [
    {
      "name": "M Barrio"
    },
    {
      "name": "J.-Ll Tamarit"
    },
    {
      "name": "R Ceolin"
    },
    {
      "name": "B Robert"
    },
    {
      "name": "M-A Perrin"
    },
    {
      "name": "Ivo B. Rietveld"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/49yzpx49x99et.bib",
  "cited_by": 0,
  "doi": "10.1016/j.ijpharm.2026.127455",
  "fulltext_url": null,
  "id": "49yzpx49x99et",
  "issns": [
    "0378-5173"
  ],
  "landing_url": "https://hal.science/hal-05795391v1",
  "language": "en",
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "hal",
      "0.chim"
    ],
    [
      "openalex",
      "2505|Crystallization and Solubility Studies"
    ]
  ],
  "openalex": "W7220371846",
  "pdf_url": "https://hal.science/hal-05795391/document",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-12",
  "publisher": "Elsevier",
  "ris": "https://research.draconitic.com/paper/49yzpx49x99et.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:55Z",
      "native_id": "hal-05795391",
      "source": "hal",
      "url": "https://hal.science/hal-05795391v1"
    }
  ],
  "subjects": [
    {
      "field": "chemistry",
      "origin": "openalex:2505|Crystallization and Solubility Studies",
      "subfield": "materials-polymers"
    }
  ],
  "title": "The pressure–temperature phase diagram of dimorphic caffeine: experiment versus topology",
  "title_text": "The pressure–temperature phase diagram of dimorphic caffeine: experiment versus topology",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:17:55Z",
  "url": "https://research.draconitic.com/paper/49yzpx49x99et",
  "venue": "International Journal of Pharmaceutics",
  "versions": []
}