Stabilisation of amorphous furosemide increases the oral drug bioavailability in rats

Line Hagner Nielsen, Thomas Rades, Anette Müllertz

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    Abstract

    A glass solution of the amorphous sodium salt of furosemide (ASSF) and polyvinylpyrrolidone (PVP) (80: 20 w/w%) was prepared by spray drying. It was investigated if PVP was able to stabilise ASSF during storage and dissolution and whether this influenced the in vivo performance of the glass solution after oral dosing to rats. The glass solution had a glass transition temperature of 121.3 +/- 0.5 degrees C, which was significantly higher than that of the pure drug (101.2 degrees C). ASSF in the glass solution was stable for at least 168 days when stored at 20 degrees C and 0% relative humidity. The glass solution exhibited fast dissolution in simulated intestinal medium, pH 6.5; the intrinsic dissolution rate was found to be 10.1 +/- 0.6 mg/cm(2)/min, which was significantly faster than the pure ASSF. When investigating the stability during dissolution in stimulated intestinal medium at pH 6.5, the ASSF in the glass solution showed signs of crystallinity after 1 min of dissolution, but crystallised to a lesser extent than pure ASSF. The stabilising effect of PVP on ASSF, led to improved relative oral bioavailability in rats of 263%, when compared to the pure ASSF. (C) 2015 Elsevier B.V. All rights reserved.
    Original languageEnglish
    JournalInternational Journal of Pharmaceutics
    Volume490
    Issue number1-2
    Pages (from-to)334-340
    Number of pages7
    ISSN0378-5173
    DOIs
    Publication statusPublished - 2015

    Keywords

    • Furosemide
    • Polyvinylpyrrolidone
    • Glass solution
    • Solid dispersion
    • Amorphous
    • Oral bioavailability

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