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Indomethacin: Effect of Diffusionless Crystal Growth on Thermal Stability during Long-Term Storage

Autoři: Svoboda Roman | Koutná Nicola | Košťálová Daniela | Krbal Miloš | Komersová Alena

Rok: 2023

Druh publikace: článek v odborném periodiku

Název zdroje: Molecules

Název nakladatele: MDPI

Místo vydání: BASEL

Strana od-do: "1568-1"-"1568-22"

Tituly:

Jazyk	Název	Abstrakt	Klíčová slova
cze	Indometacin: Efekt na difůzi nezávislého růstu krystalů na tepelnou stabilitu během dlouhodobého skladování	Diferenciální skenovací kalorimetrie a Ramanova spektroskopie byly použity pro neisotermní a izotermní studii krystalizačního chování amorfního indometacinu ve formě prášků. Byla studována zejména závislost tepelné stability těchto materiálů na dlouhodobém skladování při laboratorní tewplotě a vlhkosti v porovnání se skladováním v desikátoru při 10 °C.	amorfní indometacin; krystalizace; kinetická predikce; velikost částic; skladování
eng	Indomethacin: Effect of Diffusionless Crystal Growth on Thermal Stability during Long-Term Storage	Differential scanning calorimetry and Raman spectroscopy were used to study the non-isothermal and isothermal crystallization behavior of amorphous indomethacin powders (with particle sizes ranging from 50 to 1000 mu m) and their dependence on long-term storage conditions, either 0-100 days stored freely at laboratory ambient temperatures and humidity or placed in a desiccator at 10 degrees C. Whereas the gamma-form polymorph always dominated, the accelerated formation of the alpha-form was observed in situations of heightened mobility (higher temperature and heating rate), increased amounts of mechanically induced defects, and prolonged free-surface nucleation. A complex crystallization behavior with two separated crystal growth modes (originating from either the mechanical defects or the free surface) was identified both isothermally and nonisothermally. The diffusionless glass-crystal (GC) crystal growth was found to proceed during the long-term storage at 10 degrees C and zero humidity, at the rate of similar to 100 mu m of the gamma-form surface crystalline layer being formed in 100 days. Storage at the laboratory temperature (still below the glass transition temperature) and humidity led only to a negligible/nondetectable GC growth for the fine indomethacin powders (particle size below similar to 150 mu m), indicating a marked suppression of GC growth by the high density of mechanical defects under these conditions. The freely stored bulk material with no mechanical damage and a smooth surface exhibited zero traces of GC growth (as confirmed by microscopy) after >150 days of storage. The accuracy of the kinetic predictions of the indomethacin crystallization behavior was rather poor due to the combined influences of the mechanical defects, competing nucleation, and crystal growth processes of the two polymorphic phases as well as the GC growth complex dependence on the storage conditions within the vicinity of the glass transition temperature. Performing paire	amorphous indomethacin; crystallization; kinetic prediction; particle size; storage

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