{
  "abstract": "p. 2 Abstract Preservation of the adsorption-relevant surface state is critical for meaningful surface characterization of dehydration-sensitive pharmaceutical hydrates, because changes in hydration and surface structure may occur during sample preparation and measurement. Previous studies have demonstrated that humidity-controlled inverse gas chromatography (IGC) can prevent bulk hydrate-to-anhydrate phase transformation during specific surface area measurement. However, preservation of the bulk crystalline phase does not necessarily ensure preservation of the adsorption-relevant surface state. In this study, humidity-controlled IGC was investigated as a means of maintaining the hydration environment during surface characterization of three pharmaceutical hydrate systems: sodium saccharin dihydrate, L-cysteine hydrochloride monohydrate, and citric acid monohydrate. Hydration behavior was characterized by dynamic vapor sorption, and changes in particle morphology were examined by optical microscopy. IGC measurements were performed under controlled relative humidity using n-nonane as an adsorption probe, and BET analysis was used to estimate the probe-accessible surface area under the specified measurement conditions. The applicability of the IGC-based approach was supported by measurements of the reference material BCR-170, for which the obtained surface area was consistent with the certified value. Importantly, the adsorption-derived surface area was found to depend on sample history and elapsed time even under humidity conditions selected to maintain the hydrate state. In L-cysteine hydrochloride monohydrate, the apparent surface area decreased from 0.43 to 0.30 m2 g-1 after storage following sieving, accompanied by a substantial decrease in column pressure drop. These findings suggest that preservation of the hydrate phase alone does not ensure preservation of the adsorption-relevant surface state. Humidity-controlled IGC provides a useful approach for evaluating probe-accessible surface behavior of dehydration-sensitive pharmaceutical hydrates while minimizing perturbation of their hydration environment.",
  "abstract_shown": true,
  "affiliations": [
    "Chugai Pharmaceutical Co., Ltd.",
    "Gifu Pharmaceutical University"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 2,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Ken Yoshioka",
      "orcid": "0009-0004-9292-6675"
    },
    {
      "affs": [
        1
      ],
      "name": "Kohei Tahara"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/0ey2zxjaaj0kp.bib",
  "cited_by": 0,
  "doi": "10.26434/chemrxiv.15008132/v1",
  "fulltext_url": null,
  "id": "0ey2zxjaaj0kp",
  "issns": [],
  "landing_url": "https://chemrxiv.org/doi/full/10.26434/chemrxiv.15008132/v1",
  "language": null,
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "1607|Adsorption, diffusion, and thermodynamic properties of materials"
    ]
  ],
  "openalex": "W7204874998",
  "pdf_url": "https://chemrxiv.org/doi/pdf/10.26434/chemrxiv.15008132/v1",
  "pmcid": null,
  "pmid": null,
  "published": "2026-08-31",
  "publisher": "American Chemical Society (ACS)",
  "ris": "https://research.draconitic.com/paper/0ey2zxjaaj0kp.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:17Z",
      "native_id": "10.26434/chemrxiv.15008132",
      "source": "chemrxiv",
      "url": "https://chemrxiv.org/doi/full/10.26434/chemrxiv.15008132/v1"
    }
  ],
  "subjects": [
    {
      "field": "chemistry",
      "origin": "openalex:1607|Adsorption, diffusion, and thermodynamic properties of materials",
      "subfield": "physical"
    }
  ],
  "title": "Humidity-Controlled Inverse Gas Chromatography for Preserving the Adsorption-Relevant Surface State of Dehydration-Sensitive Pharmaceutical Hydrates",
  "title_text": "Humidity-Controlled Inverse Gas Chromatography for Preserving the Adsorption-Relevant Surface State of Dehydration-Sensitive Pharmaceutical Hydrates",
  "type": "preprint",
  "updated_at": "2026-10-30T12:17:17Z",
  "url": "https://research.draconitic.com/paper/0ey2zxjaaj0kp",
  "venue": "ChemRxiv",
  "versions": []
}