Stored amorphous samples and intrinsic dissolution testing – the interplay of crystallisation and dissolution behaviour

The recrystallisation behaviour of amorphous indomethacin and the dissolution behaviour of different solid state forms of indomethacin have been previously studied. However, the effect of crystallites developed during storage on recrystallisation during dissolution has not yet, to the best of our knowledge, been investigated. Quench cooled amorphous indomethacin stored at 30 °C and 23% or 42% relative humidity (RH) was characterised by dissolution testing, and crystallisation during storage and dissolution testing was monitored with attenuated total reflectance infrared (ATR-IR) spectroscopy and scanning electron microscopy. Freshly prepared indomethacin recrystallized to the α-form during dissolution. Particles stored at 23% RH exhibited surface crystallisation (γ form) during storage (5 days), recrystallized to the γ form during dissolution and exhibited a dissolution profile similar to the γ polymorph. Indomethacin stored at 42% RH recrystallised to the γ form. After storage (5 days), the tablet surface crystallised during dissolution to an α-γ-mixture according to FT-ATR-IR spectroscopy. After storage for 14 days, dissolution resulted in recrystallisation mostly to the γ form. This work suggests that crystallite formation in amorphous systems during storage under different conditions influences the crystallisation behaviour of the remaining amorphous material during dissolution testing.