Effect of different preparation methods on the dissolution behaviour of amorphous indomethacin

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Effect of different preparation methods on the dissolution behaviour of amorphous indomethacin. / Karmwar, Pranav; Graeser, Kirsten; Gordon, Keith C.; Strachan, Clare J.; Rades, Thomas.

In: European Journal of Pharmaceutics and Biopharmaceutics, Vol. 80, No. 2, 02.2012, p. 459-464.

Research output: Contribution to journalJournal articlepeer-review

Harvard

Karmwar, P, Graeser, K, Gordon, KC, Strachan, CJ & Rades, T 2012, 'Effect of different preparation methods on the dissolution behaviour of amorphous indomethacin', European Journal of Pharmaceutics and Biopharmaceutics, vol. 80, no. 2, pp. 459-464. https://doi.org/10.1016/j.ejpb.2011.10.006

APA

Karmwar, P., Graeser, K., Gordon, K. C., Strachan, C. J., & Rades, T. (2012). Effect of different preparation methods on the dissolution behaviour of amorphous indomethacin. European Journal of Pharmaceutics and Biopharmaceutics, 80(2), 459-464. https://doi.org/10.1016/j.ejpb.2011.10.006

Vancouver

Karmwar P, Graeser K, Gordon KC, Strachan CJ, Rades T. Effect of different preparation methods on the dissolution behaviour of amorphous indomethacin. European Journal of Pharmaceutics and Biopharmaceutics. 2012 Feb;80(2):459-464. https://doi.org/10.1016/j.ejpb.2011.10.006

Author

Karmwar, Pranav ; Graeser, Kirsten ; Gordon, Keith C. ; Strachan, Clare J. ; Rades, Thomas. / Effect of different preparation methods on the dissolution behaviour of amorphous indomethacin. In: European Journal of Pharmaceutics and Biopharmaceutics. 2012 ; Vol. 80, No. 2. pp. 459-464.

Bibtex

@article{ea8bcda8ea274893a06089c7cbde99f0,
title = "Effect of different preparation methods on the dissolution behaviour of amorphous indomethacin",
abstract = "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.",
keywords = "Amorphous, Cooling rate, Cryo-milling, Dissolution behaviour, Indomethacin, Solution-mediated solid state transformation",
author = "Pranav Karmwar and Kirsten Graeser and Gordon, {Keith C.} and Strachan, {Clare J.} and Thomas Rades",
year = "2012",
month = feb,
doi = "10.1016/j.ejpb.2011.10.006",
language = "English",
volume = "80",
pages = "459--464",
journal = "European Journal of Pharmaceutics and Biopharmaceutics",
issn = "0939-6411",
publisher = "Elsevier",
number = "2",

}

RIS

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 -

ID: 299415829