A slow cooling rate of indomethacin melt spatially confined in microcontainers increases the physical stability of the amorphous drug without influencing its biorelevant dissolution behaviour

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    Abstract

    Amorphous indomethacin was prepared by melting the γ-form of indomethacin, spatially confined within microcontainers (inner diameter of 223 μm), followed by
    cooling of the melt at a rate of 14, 23 or 36 K/min. The physical stability of the amorphous indomethacin within microcontainers was investigated using Raman microscopy. Furthermore, the dissolution behaviour of confined amorphous
    indomethacin was evaluated in biorelevant intestinal media at pH 6.5. After 30 days of storage, 10.3±1.2 % of the amorphous indomethacin cooled at 14 K/min and confined within microcontainers was found to be crystalline. When
    the melt of indomethacin was cooled at 23 or 36 K/min, 20.7±1.5 and 31.0±2.6%of the indomethacin were found to be crystalline after storage for 30 days. Scanning electron microscopy showed a smooth surface of amorphous indomethacin within the microcontainers when cooling the melt at 14 K/min, whereas cracks and an uneven surface were observed when cooling at rates of 23 and 36 K/min. The uneven surface is hypothesised to be the main reason for the lower physical stability, as the cracks could act as nucleation sites for crystal growth. The rate of cooling was not seen to have any effect on the dissolution of amorphous indomethacin from the microcontainers.
    Original languageEnglish
    JournalDrug Delivery and Translational Research
    Volume4
    Issue number3
    Pages (from-to)268-274
    ISSN2190-393X
    DOIs
    Publication statusPublished - 2013

    Keywords

    • Amorphous indomethacin
    • Amorphous form preparation
    • Physical stability
    • Biorelevant dissolution
    • Raman microscopy

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