Investigation of physical properties and stability of indomethacin-cimetidine and naproxen-cimetidine co-amorphous systems prepared by quench cooling, coprecipitation and ball milling
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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.
|Journal||Journal of Pharmacy and Pharmacology|
|Number of pages||10|
|Publication status||Published - Jan 2016|