The impact of surface- and nano-crystallisation on the detected amorphous content and the dissolution behaviour of amorphous indomethacin

TY - JOUR

T1 - The impact of surface- and nano-crystallisation on the detected amorphous content and the dissolution behaviour of amorphous indomethacin

AU - Priemel, Petra A.

AU - Grohganz, Holger

AU - Gordon, Keith C.

AU - Rades, Thomas

AU - Strachan, Clare

PY - 2012/9

Y1 - 2012/9

N2 - The crystallinity and physical stability of amorphous drugs has previously been studied using different analytical techniques. However, the effect of the measurement method on observed crystallinity and its importance for critical quality attributes, such as dissolution, has not yet been widely investigated. The aim of this study was to (i) qualitatively analyse and understand the recrystallisation behaviour of amorphous indomethacin during storage, (ii) quantify the amorphous content during storage with complementary analytical techniques and (iii) investigate the relationship between observed recrystallisation behaviour and dissolution behaviour. Quench cooled indomethacin was stored and the samples were visualised by scanning electron microscopy to gain spatially resolved information about the recrystallisation behaviour. Crystallisation was quantified by Fourier transform attenuated total reflectance infrared (FT-ATR-IR) spectroscopy, differential scanning calorimetry and X-ray powder diffraction. These techniques resulted in different observed recrystallisation profiles. The physicochemical phenomena detected and sampling geometry for each technique together with the sample recrystallising from the surface and appearance of nano-crystals were used to explain the differences. The dissolution behaviour at the observed recrystallisation endpoints for the different analytical techniques revealed that FT-ATR-IR spectroscopy predicted the changes in dissolution behaviour due to crystallisation best.

AB - The crystallinity and physical stability of amorphous drugs has previously been studied using different analytical techniques. However, the effect of the measurement method on observed crystallinity and its importance for critical quality attributes, such as dissolution, has not yet been widely investigated. The aim of this study was to (i) qualitatively analyse and understand the recrystallisation behaviour of amorphous indomethacin during storage, (ii) quantify the amorphous content during storage with complementary analytical techniques and (iii) investigate the relationship between observed recrystallisation behaviour and dissolution behaviour. Quench cooled indomethacin was stored and the samples were visualised by scanning electron microscopy to gain spatially resolved information about the recrystallisation behaviour. Crystallisation was quantified by Fourier transform attenuated total reflectance infrared (FT-ATR-IR) spectroscopy, differential scanning calorimetry and X-ray powder diffraction. These techniques resulted in different observed recrystallisation profiles. The physicochemical phenomena detected and sampling geometry for each technique together with the sample recrystallising from the surface and appearance of nano-crystals were used to explain the differences. The dissolution behaviour at the observed recrystallisation endpoints for the different analytical techniques revealed that FT-ATR-IR spectroscopy predicted the changes in dissolution behaviour due to crystallisation best.

U2 - 10.1016/j.ejpb.2012.05.012

DO - 10.1016/j.ejpb.2012.05.012

M3 - Journal article

C2 - 22683936

SN - 0939-6411

VL - 82

SP - 187

EP - 193

JO - European Journal of Pharmaceutics and Biopharmaceutics

JF - European Journal of Pharmaceutics and Biopharmaceutics

IS - 1

ER -