Investigation of physical properties and stability of indomethacin-cimetidine and naproxen-cimetidine co-amorphous systems prepared by quench cooling, coprecipitation and ball milling

Ai Wei Lim, Korbinian Löbmann, Holger Grohganz, Thomas Rades, Norman Chieng

    34 Citationer (Scopus)

    Abstract

    OBJECTIVES: The objective was to characterize the structural behaviour of indomethacin-cimetidine and naproxen-cimetidine co-amorphous systems (1 : 1 molar ratio) prepared by quench cooling, co-evaporation and ball milling.

    METHODS: Powder X-ray diffraction (PXRD) and DSC were used to characterise the samples. Structural relaxation (i.e. molecular mobility) behaviour was obtained from the Kohlrausch-Williams-Watts (KWW) relationship.

    KEY FINDINGS: A glass transition temperature (Tg ), on average 20 °C higher than the predicted Tg (calculated from the Fox equation), was observed in all samples. The structural relaxation was dependent on the preparative methods. At a storage temperature of 40 °C, a comparatively higher molecular mobility was observed in indomethacin-cimetidine samples prepared by ball milling (ln τ(β) = 0.8), while similar molecular mobility was found for the same sample prepared by quench cooling (ln τ(β) = 2.4) and co-evaporation (ln τ(β) = 2.5). In contrast, molecular mobility of the naproxen-cimetidine samples followed the order co-evaporation (ln τ(β) = 0.8), quench cooling (ln τ(β) = 1.6) and ball milling (ln τ(β) = 1.8).

    CONCLUSION: The estimated relaxation times by the DSC-KWW method suggest that different preparative methods resulted in a variation of structural characteristics. Despite the differences in molecular mobility, all sample remained co-amorphous for up to 7 months.

    OriginalsprogEngelsk
    TidsskriftJournal of Pharmacy and Pharmacology
    Vol/bind68
    Udgave nummer1
    Sider (fra-til)36-45
    Antal sider10
    ISSN0022-3573
    DOI
    StatusUdgivet - 1 jan. 2016

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