Solid-state nuclear magnetic resonance study of the physical stability of electrospun drug and polymer solid solutions

Authors

  • Blair Kathryn Brettmann,

    1. Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts
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  • Allan S. Myerson,

    1. Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts
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  • Bernhardt L. Trout

    Corresponding author
    1. Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts
    • Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts. (Telephone: +617-230-2319; Fax: +617-253-2272
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Abstract

A major challenge in utilizing the amorphous form of an active pharmaceutical ingredient (API) in a final oral dosage form is preventing crystallization over time and ensuring stability. One method to improve stability is lowering the mobility of an API by formulating as a solid solution with an excipient. In this work, we use electrospinning to prepare solid solutions of API, aliskiren (SPP) or indomethacin (IND), and a polymer, polyvinylpyrrolidone (PVP). The stability of the solid solutions over 6-month storage in a desiccator at 40°C was investigated. Using X-ray diffraction and differential scanning calorimetry, it was determined that no crystals were present in the four formulations tested—1:1 SPP–PVP, 4:1 SPP–PVP, 1:1 IND–PVP, and 2:1 IND–PVP at any time. Solid-state nuclear magnetic resonance relaxation time measurements were used to determine whether phase separation of the API and polymer occurred during the study period. It was found that all formulations remained homogeneous down to at least a 2–10 nm length scale, indicating that for these APIs, electrospinning is an acceptable method for forming stable amorphous solid solutions. © 2012 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 101:2185–2193, 2012

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