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Release-modulating factors strongly affecting steroid diffusion from silicone elastomer

Authors

  • Harold A. Nash,

    Corresponding author
    1. Center for Biomedical Research, Population Council, 1230 York Avenue, New York, New York 10021
    • Center for Biomedical Research, Population Council, 1230 York Avenue, New York, New York 10021. Telephone: 212-327-8719; Fax: 212-327-7678
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  • Dale N. Robertson,

    1. Center for Biomedical Research, Population Council, 1230 York Avenue, New York, New York 10021
    Current affiliation:
    1. 29783 Canterbury Circle, Evergreen, CO 80439.
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  • Simone J. Evans

    1. Center for Biomedical Research, Population Council, 1230 York Avenue, New York, New York 10021
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  • Harold A. Nash and Dale N. Robertson are retired.

Abstract

Investigations were undertaken to determine the cause of decreases over time in the release rate from levonorgestrel (LNG) implants consisting of silicone elastomer tubing filled with crystalline steroid. Emptying and refilling with the same steroid partially restored release rate. Surprisingly, a further increment in release rates was attained if the tubing was briefly irrigated with methanol before refill. Fractional crystallization showed that release-modulating factors could be concentrated in mother liquors and were initially present as impurities. Boiling LNG in ethanol or methanol produced a number of release-modulating factors of which the most prominent was also found in one production lot of LNG. It was identified as 6β-hydroxy-levonorgestrel (6β-OH-LNG). Added to LNG at the 2% level, 6β-OH-LNG decreased the release rate by 27%. © 2004 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 93:2420–2430, 2004

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