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The Stabilization of Amorphous Zopiclone in an Amorphous Solid Dispersion

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Abstract

Zopiclone is a poorly soluble psychotherapeutic agent. The aim of this study was to prepare and characterize an amorphous form of zopiclone as well as the characterization and performance of a stable amorphous solid dispersion. The amorphous form was prepared by the well-known method of quench-cooling of the melt. The solid dispersion was prepared by a solvent evaporation method of zopiclone, polyvinylpyrrolidone-25 (PVP-25), and methanol, followed by freeze-drying. The physico-chemical properties and stability of amorphous zopiclone and the solid dispersion was studied using differential scanning calorimetry (DSC), infrared spectroscopy (FT-IR), thermogravimetric analysis (TGA), scanning electron microscopy (SEM), hot-stage microscopy (HSM), X-ray diffractometry (XRD), solubility, and dissolution studies. The zopiclone amorphous solid-state form was determined to be a fragile glass; it was concluded that the stability of the amorphous form is influenced by both temperature and water. Exposure of amorphous zopiclone to moisture results in rapid transformation of the amorphous form to the crystalline dihydrated form. In comparison, the amorphous solid dispersion proved to be more stable with increased aqueous solubility.

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Acknowledgments

The authors are grateful to the North-West University, South Africa (Potchefstroom Campus as well as the National Research Foundation (NRF) of South Africa for research support.

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Any opinion, findings, and conclusions or recommendations expressed in this material are those of the authors and therefore the NRF do not accept any liability thereto.

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Authors and Affiliations

  1. Centre of Excellence for Pharmaceutical Sciences, Faculty of Health Sciences, Potchefstroom Campus, North-West University, 2520, Potchefstroom, South Africa

    Marnus Milne, Wilna Liebenberg & Marique Aucamp

Authors
  1. Marnus Milne
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  2. Wilna Liebenberg
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  3. Marique Aucamp
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Correspondence to Marique Aucamp.

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Milne, M., Liebenberg, W. & Aucamp, M. The Stabilization of Amorphous Zopiclone in an Amorphous Solid Dispersion. AAPS PharmSciTech 16, 1190–1202 (2015). https://doi.org/10.1208/s12249-015-0302-4

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