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Effects of dissolved state of aminoalkyl methacrylate copolymer E/HCl on solubility enhancement effect for poorly water-soluble drugs

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Abstract

Eudragit® E/HCl salt (E–SD) displays a good antireprecipitation effect on solid dispersion formulations of poorly water-soluble drugs. To elucidate the mechanism underlying the antireprecipitation effect of E–SD, a study on supersaturation was conducted using a dissolution test method with test fluids at varying pH and ionic strength values. Both pH and ionic strength of the test fluid were shown to influence the antireprecipitation effect of E–SD; a strong antireprecipitation effect was observed at a neutral pH (pH 6∼7) and an ionic strength of 0.1 to 1.0. To investigate E–SD in its dissolved state in each test fluid, fluorescence measurement using pyrene as a probe molecule and dynamic light-scattering (DLS) measurement were conducted. The total fluorescence intensity of pyrene increased with increasing E–SD concentrations. Further, small nanoparticles were observed using DLS measurement. These results suggest that E–SD may form a micelle-like structure in the dissolved test fluid.

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Authors and Affiliations

  1. Pharmaceutical Research and Technology Labs, Astellas Pharma Inc., 180 Ozumi, Yaizu, Shizuoka, 425-0072, Japan

    Takatsune Yoshida, Ippei Kurimoto, Hiroyuki Umejima, Shunsuke Watanabe & Kazuhiro Sako

  2. Department of Materials Science and Technology, Graduate School of Industrial Science and Technology, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba, 278-8510, Japan

    Takatsune Yoshida & Akihiko Kikuchi

Authors
  1. Takatsune Yoshida
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  2. Ippei Kurimoto
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  3. Hiroyuki Umejima
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  4. Shunsuke Watanabe
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  5. Kazuhiro Sako
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  6. Akihiko Kikuchi
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Correspondence to Takatsune Yoshida.

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Yoshida, T., Kurimoto, I., Umejima, H. et al. Effects of dissolved state of aminoalkyl methacrylate copolymer E/HCl on solubility enhancement effect for poorly water-soluble drugs. Colloid Polym Sci 291, 1191–1199 (2013). https://doi.org/10.1007/s00396-012-2848-y

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  • DOI: https://doi.org/10.1007/s00396-012-2848-y

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