TY - JOUR
T1 - Effect of different preparation methods on the dissolution behaviour of amorphous indomethacin
AU - Karmwar, Pranav
AU - Graeser, Kirsten
AU - Gordon, Keith C.
AU - Strachan, Clare J.
AU - Rades, Thomas
PY - 2012/2
Y1 - 2012/2
N2 - The aim of this study was to investigate whether amorphous indomethacin samples prepared using different preparative techniques and processing parameters exhibit different structural and thermodynamic characteristics and whether these differences can be correlated to their dissolution behaviour. Samples were prepared either by cooling the drug melt at different cooling rates or by cryo-milling the drug for different milling times. The resulting amorphous materials were characterised using X-ray diffraction, Raman spectroscopy and polarising light microscopy. All samples were entirely X-ray amorphous, except for the sample cryo-milled for 15 min, which exhibited residual crystallinity. The shape of the halos in the diffractograms, however, varied depending on the preparation method and processing parameters, suggesting structural variations in the near order of the molecules between the prepared amorphous forms. This finding was supported by principal component analysis of the Raman spectra, as the samples clustered in the scores plot according to processing parameters for both of the preparative methods used. When investigating the dissolution behaviour, the samples cooled at different cooling rates showed no significant differences in their dissolution profiles and dissolution rates (≈0.55 μg/ml/cm 2). In contrast, for cryo-milled samples, dissolution rate depended on the milling time, with samples milled for 120, 180 and 240 min, showing significantly increased dissolution rates of 0.28, 0.48 and 0.59 μg/ml/cm 2, respectively, when compared to crystalline indomethacin (≈0.06 and 0.05 μg/ml/cm 2 for α and γ-indomethacin, respectively). The milling processes appear to continue to affect the degree of disorder in the solid material, enhancing its dissolution rate, although all samples milled for >30 min were X-ray amorphous. Thus, choosing the right preparation technique and parameters for preparing amorphous solids is critical for producing materials with enhanced dissolution profiles.
AB - The aim of this study was to investigate whether amorphous indomethacin samples prepared using different preparative techniques and processing parameters exhibit different structural and thermodynamic characteristics and whether these differences can be correlated to their dissolution behaviour. Samples were prepared either by cooling the drug melt at different cooling rates or by cryo-milling the drug for different milling times. The resulting amorphous materials were characterised using X-ray diffraction, Raman spectroscopy and polarising light microscopy. All samples were entirely X-ray amorphous, except for the sample cryo-milled for 15 min, which exhibited residual crystallinity. The shape of the halos in the diffractograms, however, varied depending on the preparation method and processing parameters, suggesting structural variations in the near order of the molecules between the prepared amorphous forms. This finding was supported by principal component analysis of the Raman spectra, as the samples clustered in the scores plot according to processing parameters for both of the preparative methods used. When investigating the dissolution behaviour, the samples cooled at different cooling rates showed no significant differences in their dissolution profiles and dissolution rates (≈0.55 μg/ml/cm 2). In contrast, for cryo-milled samples, dissolution rate depended on the milling time, with samples milled for 120, 180 and 240 min, showing significantly increased dissolution rates of 0.28, 0.48 and 0.59 μg/ml/cm 2, respectively, when compared to crystalline indomethacin (≈0.06 and 0.05 μg/ml/cm 2 for α and γ-indomethacin, respectively). The milling processes appear to continue to affect the degree of disorder in the solid material, enhancing its dissolution rate, although all samples milled for >30 min were X-ray amorphous. Thus, choosing the right preparation technique and parameters for preparing amorphous solids is critical for producing materials with enhanced dissolution profiles.
KW - Amorphous
KW - Cooling rate
KW - Cryo-milling
KW - Dissolution behaviour
KW - Indomethacin
KW - Solution-mediated solid state transformation
UR - http://www.scopus.com/inward/record.url?scp=84856595812&partnerID=8YFLogxK
U2 - 10.1016/j.ejpb.2011.10.006
DO - 10.1016/j.ejpb.2011.10.006
M3 - Journal article
C2 - 22019529
AN - SCOPUS:84856595812
VL - 80
SP - 459
EP - 464
JO - European Journal of Pharmaceutics and Biopharmaceutics
JF - European Journal of Pharmaceutics and Biopharmaceutics
SN - 0939-6411
IS - 2
ER -