biostudies-literatureMartins ICBDanmarks Frie Forskningsfond11447-11455https://www.ebi.ac.uk/biostudies/studies/S-EPMC10599472biostudies-literatureUnknown14(41)Polyamorphism has been a controversial and highly debated solid-state phenomenon in both material and pharmaceutical communities. Although some evidence of this fascinating phenomenon has been reported for several inorganic systems, and more recently also for a few organic compounds, the occurrence of polyamorphism is poorly understood and the molecular-level organization of polyamorphic forms is still unknown. Here we have investigated the occurrence of polyamorphism and polyamorphic interconversions in hydrochlorothiazide (HCT), using both experimental and computational methods. Three distinct HCT polyamorphs, presenting distinct physical and thermal stabilities as well as distinct relaxation properties, were systematically prepared using spray-drying (SD), quench-cooling (QC) and ball mChemical scienceUnveiling polyamorphism and polyamorphic interconversions in pharmaceuticals: the peculiar case of hydrochlorothiazide.PMC105994720135-00103AFrederiksen OARades TJeppesen HSMartins ICBMadsen AOCorreia AJensen KMOLarsen ASfalseUnveiling polyamorphism and polyamorphic interconversions in pharmaceuticals: the peculiar case of hydrochlorothiazide.Polyamorphism has been a controversial and highly debated solid-state phenomenon in both material and pharmaceutical communities. Although some evidence of this fascinating phenomenon has been reported for several inorganic systems, and more recently also for a few organic compounds, the occurrence of polyamorphism is poorly understood and the molecular-level organization of polyamorphic forms is still unknown. Here we have investigated the occurrence of polyamorphism and polyamorphic interconversions in hydrochlorothiazide (HCT), using both experimental and computational methods. Three distinct HCT polyamorphs, presenting distinct physical and thermal stabilities as well as distinct relaxation properties, were systematically prepared using spray-drying (SD), quench-cooling (QC) and ball m2023-01-01T00:00:00Z2023 Oct2025-04-19T17:02:44.446Z2025-02-19T03:05:20.701ZS-EPMC105994723788610210.1039/d3sc02802j