{
  "abstract": "Background: Continuous pharmaceutical crystallization requires simultaneous control of supersaturation, particle attributes, polymorphic form, fouling, and downstream processability. Accordingly, single-stage and two-stage mixed-suspension mixed-product-removal (MSMPR) crystallization systems were developed and compared for the controlled production of the target crystalline polymorphs: paracetamol Form I and carbamazepine Form III.\n\nMethods: Equilibrium solubility and metastable-zone limits were determined before continuous operation. Four critical process parameters, residence time, relative supersaturation, continuous seed loading, and power input per unit volume, were evaluated using independent four-factor Box–Behnken designs. Response-surface optimization, stagewise population-balance modeling, multimodal process analytical technology, and matched configuration comparisons were performed at equal total active volume and overall residence time.\n\nResults: For both APIs, longer residence time increased median particle size toward the prespecified product-size ranges, narrowed particle-size distributions, and improved target-polymorph content, but reduced space-time yield. Higher supersaturation increased recovery and productivity for both APIs while broadening distributions and reducing polymorphic selectivity. Externally validated population-balance models achieved R2 values of 0.894–0.943 and normalized RMSE values of 1.8%–8.8%. Relative to single-stage operation, two-stage MSMPR increased D50 by 15.8% for paracetamol and 13.6% for carbamazepine, reduced PSD span by 14.6% and 16.9%, and decreased fouling by 42.4% and 45.8%, respectively. The larger, narrower particles were beneficial because filtration time declined by 26.3% for paracetamol and 34.4% for carbamazepine, while chemical purity and mass-balance closure were preserved.\n\nConclusion: At matched active volume and overall residence time, staged supersaturation generation suppressed fines, improved particle uniformity and morphology, and reduced fouling and filtration time without compromising chemical or solid-state quality. These results identify controlled supersaturation distribution, not additional crystallizer capacity, as the principal benefit of two-stage MSMPR operation for the two APIs studied.",
  "abstract_shown": true,
  "affiliations": [
    "Higher Vocational and Technical College, Wenshan University , , ,"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 1,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Funeng Tan"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/5ed15evw8t83s.bib",
  "cited_by": 0,
  "doi": "10.3389/fchem.2026.1947756",
  "fulltext_url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13721075/?tool=EBI",
  "id": "5ed15evw8t83s",
  "issns": [
    "2296-2646"
  ],
  "landing_url": "https://europepmc.org/article/PMC/PMC13721075",
  "language": "eng",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Original Research"
    ],
    [
      "openalex",
      "2505|Crystallization and Solubility Studies"
    ]
  ],
  "openalex": "W7222745380",
  "pdf_url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13721075/pdf/?tool=EBI",
  "pmcid": "PMC13721075",
  "pmid": "42964682",
  "published": "2026-10-16",
  "publisher": "Frontiers Media SA",
  "ris": "https://research.draconitic.com/paper/5ed15evw8t83s.ris",
  "sources": [
    {
      "first_seen": "2026-10-31T12:21:36Z",
      "native_id": "PMC:PMC13721075",
      "source": "europepmc",
      "url": "https://europepmc.org/article/PMC/PMC13721075"
    },
    {
      "first_seen": "2026-11-03T12:21:49Z",
      "native_id": "PMC13721075",
      "source": "pmc",
      "url": "https://doi.org/10.3389/fchem.2026.1947756"
    }
  ],
  "subjects": [
    {
      "field": "chemistry",
      "origin": "openalex:2505|Crystallization and Solubility Studies",
      "subfield": "materials-polymers"
    }
  ],
  "title": "Continuous crystallization of pharmaceutical compounds in mixed suspension mixed product removal systems",
  "title_text": "Continuous crystallization of pharmaceutical compounds in mixed suspension mixed product removal systems",
  "type": "peer-reviewed",
  "updated_at": "2026-11-03T12:21:49Z",
  "url": "https://research.draconitic.com/paper/5ed15evw8t83s",
  "venue": "Frontiers in chemistry",
  "versions": []
}