Prediction of polymorphic transformations of paracetamol in solid dispersions

Mohammed Maniruzzaman, Muhammad T. Islam, Hiren G. Moradiya, Sheelagh A. Halsey, Ian J. Slipper, Babur Z. Chowdhry, Martin J. Snowden, Dennis Douroumis

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

A novel approach employing variable-temperature X-ray powder diffraction (VTXRPD) was used to exploit its suitability as an off-line predictive tool to study the polymorphic transformations of paracetamol (PMOL) in melt-extruded hydrophilic polymer matrices. Physical mixtures (PMs) and extruded formulations of PMOL with either polyvinyl caprolactam graft copolymer (Soluplus®) or vinylpyrrolidone–vinyl acetate copolymer (Kollidon®) in the solid state were characterized by using differential scanning calorimetry, hot-stage microscopy, and scanning electron microscopy. The experimental findings from VTXRPD showed that the stable Form I (monoclinic) of PMOL transformed to the metastable polymorph Form II (orthorhombic) at temperatures varying from 112°C to 120°C, in both the PMs and extrudates suggesting an effect of both temperature and identity of the polymers. The findings obtained from VTXRD analysis for both the PMs and the extruded formulations were confirmed by in-line near-infrared (NIR) monitoring during the extrusion processing. In the NIR study, PMOL underwent the same pattern of polymorphic transformations as those detected using VTXPRD. The results of this study suggest that VTXRPD can be used to predict the polymorphic transformation of drugs in polymer matrices during extrusion processing and provides a better understanding of extrusion processing parameters.
Original languageEnglish
Pages (from-to)1819-1828
Number of pages10
JournalJournal of Pharmaceutical Sciences
Volume103
Issue number6
Early online date30 Apr 2014
DOIs
Publication statusPublished - 1 Jun 2014

Fingerprint

Acetaminophen
Powder Diffraction
Temperature
X-Ray Diffraction
Polymers
Caprolactam
Polyvinyls
Povidone
Differential Scanning Calorimetry
Electron Scanning Microscopy
Microscopy
Acetates
Transplants
Pharmaceutical Preparations

Keywords

  • polymorphs
  • crystals
  • drug delivery
  • polynorphism
  • near-infrared spectroscopy
  • extrudates
  • caprolactam
  • variable-temperature XRPD
  • transformation

Cite this

Maniruzzaman, M., Islam, M. T., Moradiya, H. G., Halsey, S. A., Slipper, I. J., Chowdhry, B. Z., ... Douroumis, D. (2014). Prediction of polymorphic transformations of paracetamol in solid dispersions. Journal of Pharmaceutical Sciences, 103(6), 1819-1828. https://doi.org/10.1002/jps.23992
Maniruzzaman, Mohammed ; Islam, Muhammad T. ; Moradiya, Hiren G. ; Halsey, Sheelagh A. ; Slipper, Ian J. ; Chowdhry, Babur Z. ; Snowden, Martin J. ; Douroumis, Dennis. / Prediction of polymorphic transformations of paracetamol in solid dispersions. In: Journal of Pharmaceutical Sciences. 2014 ; Vol. 103, No. 6. pp. 1819-1828.
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Maniruzzaman, M, Islam, MT, Moradiya, HG, Halsey, SA, Slipper, IJ, Chowdhry, BZ, Snowden, MJ & Douroumis, D 2014, 'Prediction of polymorphic transformations of paracetamol in solid dispersions', Journal of Pharmaceutical Sciences, vol. 103, no. 6, pp. 1819-1828. https://doi.org/10.1002/jps.23992

Prediction of polymorphic transformations of paracetamol in solid dispersions. / Maniruzzaman, Mohammed; Islam, Muhammad T.; Moradiya, Hiren G.; Halsey, Sheelagh A.; Slipper, Ian J.; Chowdhry, Babur Z.; Snowden, Martin J.; Douroumis, Dennis.

In: Journal of Pharmaceutical Sciences, Vol. 103, No. 6, 01.06.2014, p. 1819-1828.

Research output: Contribution to journalArticle

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AU - Maniruzzaman, Mohammed

AU - Islam, Muhammad T.

AU - Moradiya, Hiren G.

AU - Halsey, Sheelagh A.

AU - Slipper, Ian J.

AU - Chowdhry, Babur Z.

AU - Snowden, Martin J.

AU - Douroumis, Dennis

PY - 2014/6/1

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N2 - A novel approach employing variable-temperature X-ray powder diffraction (VTXRPD) was used to exploit its suitability as an off-line predictive tool to study the polymorphic transformations of paracetamol (PMOL) in melt-extruded hydrophilic polymer matrices. Physical mixtures (PMs) and extruded formulations of PMOL with either polyvinyl caprolactam graft copolymer (Soluplus®) or vinylpyrrolidone–vinyl acetate copolymer (Kollidon®) in the solid state were characterized by using differential scanning calorimetry, hot-stage microscopy, and scanning electron microscopy. The experimental findings from VTXRPD showed that the stable Form I (monoclinic) of PMOL transformed to the metastable polymorph Form II (orthorhombic) at temperatures varying from 112°C to 120°C, in both the PMs and extrudates suggesting an effect of both temperature and identity of the polymers. The findings obtained from VTXRD analysis for both the PMs and the extruded formulations were confirmed by in-line near-infrared (NIR) monitoring during the extrusion processing. In the NIR study, PMOL underwent the same pattern of polymorphic transformations as those detected using VTXPRD. The results of this study suggest that VTXRPD can be used to predict the polymorphic transformation of drugs in polymer matrices during extrusion processing and provides a better understanding of extrusion processing parameters.

AB - A novel approach employing variable-temperature X-ray powder diffraction (VTXRPD) was used to exploit its suitability as an off-line predictive tool to study the polymorphic transformations of paracetamol (PMOL) in melt-extruded hydrophilic polymer matrices. Physical mixtures (PMs) and extruded formulations of PMOL with either polyvinyl caprolactam graft copolymer (Soluplus®) or vinylpyrrolidone–vinyl acetate copolymer (Kollidon®) in the solid state were characterized by using differential scanning calorimetry, hot-stage microscopy, and scanning electron microscopy. The experimental findings from VTXRPD showed that the stable Form I (monoclinic) of PMOL transformed to the metastable polymorph Form II (orthorhombic) at temperatures varying from 112°C to 120°C, in both the PMs and extrudates suggesting an effect of both temperature and identity of the polymers. The findings obtained from VTXRD analysis for both the PMs and the extruded formulations were confirmed by in-line near-infrared (NIR) monitoring during the extrusion processing. In the NIR study, PMOL underwent the same pattern of polymorphic transformations as those detected using VTXPRD. The results of this study suggest that VTXRPD can be used to predict the polymorphic transformation of drugs in polymer matrices during extrusion processing and provides a better understanding of extrusion processing parameters.

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KW - crystals

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KW - polynorphism

KW - near-infrared spectroscopy

KW - extrudates

KW - caprolactam

KW - variable-temperature XRPD

KW - transformation

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DO - 10.1002/jps.23992

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SP - 1819

EP - 1828

JO - Journal of Pharmaceutical Sciences

JF - Journal of Pharmaceutical Sciences

SN - 0022-3549

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ER -

Maniruzzaman M, Islam MT, Moradiya HG, Halsey SA, Slipper IJ, Chowdhry BZ et al. Prediction of polymorphic transformations of paracetamol in solid dispersions. Journal of Pharmaceutical Sciences. 2014 Jun 1;103(6):1819-1828. https://doi.org/10.1002/jps.23992