Effect of temperature and moisture on the miscibility of amorphous dispersions of felodipine and poly(vinyl pyrrolidone)

Authors

  • Patrick J. Marsac,

    1. Department of Industrial and Physical Pharmacy, School of Pharmacy, Purdue University, West Lafayette, Indiana 47907
    2. Phase Definition and Materials Science, Merck & Co., Inc., West Point, Pennsylvania 19486
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  • Alfred C. F. Rumondor,

    1. Department of Industrial and Physical Pharmacy, School of Pharmacy, Purdue University, West Lafayette, Indiana 47907
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  • David E. Nivens,

    1. Department of Food Science, Purdue University, 745 Agriculture Mall Drive, W. Lafayette, Indiana 47907
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  • Umesh S. Kestur,

    1. Department of Industrial and Physical Pharmacy, School of Pharmacy, Purdue University, West Lafayette, Indiana 47907
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  • Lia Stanciu,

    1. School of Material Engineering, Purdue University, West Lafayette, Indiana 47907
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  • Lynne S. Taylor

    Corresponding author
    1. Department of Industrial and Physical Pharmacy, School of Pharmacy, Purdue University, West Lafayette, Indiana 47907
    • Department of Industrial and Physical Pharmacy, School of Pharmacy, Purdue University, West Lafayette, Indiana 47907. Telephone: +1-755-496-6614; Fax: +1-755-494-6545.
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Abstract

The physical stability of amorphous molecular level solid dispersions will be influenced by the miscibility of the components. The goal of this work was to understand the effects of temperature and relative humidity on the miscibility of a model amorphous solid dispersion. Infrared spectroscopy was used to evaluate drug–polymer hydrogen bonding interactions in amorphous solid dispersions of felodipine and poly(vinyl pyrrolidone) (PVP). Samples were analyzed under stressed conditions: high temperature and high relative humidity. The glass transition temperature (Tg) of select systems was studied using differential scanning calorimetry (DSC). Atomic force microscopy (AFM) and transmission electron microscopy (TEM) were used to further investigate moisture-induced changes in solid dispersions. Felodipine-PVP solid dispersions showed evidence of adhesive hydrogen bonding interactions at all compositions studied. The drug–polymer intermolecular interactions were weakened and/or less numerous on increasing the temperature, but persisted up to the melting temperature of the drug. Changes in the hydrogen bonding interactions were found to be reversible with changes in temperature. In contrast, the introduction of water into amorphous molecular level solid dispersions at room temperature irreversibly disrupted interactions between the drug and the polymer resulting in amorphous-amorphous phase separation followed by crystallization. DSC, AFM, and TEM results provided further evidence for the occurrence of moisture induced immiscibility. In conclusion, it appears that felodipine-PVP solid dispersions are susceptible to moisture-induced immiscibility when stored at a relative humidity ≥75%. In contrast, the solid dispersions remained miscible on heating. © 2009 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 99:169–185, 2010

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