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Interaction between indometacin and beta-cyclodextrin

J Szejtli, L Szente

    Die Pharmazie
    |October 1, 1981
    PubMed
    Summary
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    CHINOIN-137, an indometacin and beta-cyclodextrin complex, enhances drug dissolution and absorption. Oral administration in rats showed a 25% increase in indometacin blood levels and improved intestinal absorption.

    Area of Science:

    • Pharmaceutical Sciences
    • Drug Delivery Systems
    • Physical Chemistry

    Background:

    • Indometacin is a nonsteroidal anti-inflammatory drug (NSAID) with limited aqueous solubility.
    • Beta-cyclodextrin is a cyclic oligosaccharide commonly used to improve the solubility and bioavailability of poorly soluble drugs.
    • Complexation with cyclodextrins can alter drug properties, potentially enhancing therapeutic efficacy.

    Purpose of the Study:

    • To characterize CHINOIN-137, a novel complex of indometacin and beta-cyclodextrin.
    • To evaluate the dissolution properties and aqueous stability of CHINOIN-137.
    • To assess the in vivo pharmacokinetic and intestinal absorption profile of CHINOIN-137 compared to indometacin alone.

    Main Methods:

    • Solid-state analysis including thermal analysis, mass spectrometry, and X-ray powder diffraction.

    Related Experiment Videos

  • In vitro dissolution studies in aqueous media.
  • Diffusion tests and chiroptical property analysis to confirm complex formation and stability.
  • In vivo oral administration studies in rats with blood level monitoring.
  • "In loco" intestinal absorption studies using radiolabeled indometacin and its complex.

    • Main Results:

    • Solid-state analyses did not indicate a well-defined crystalline complex.
    • CHINOIN-137 exhibited significantly enhanced dissolution in water compared to indometacin alone.
    • Diffusion tests and chiroptical properties confirmed the formation of a stable inclusion complex in aqueous solution.
    • Oral administration of CHINOIN-137 to rats resulted in approximately 25% higher indometacin blood levels.
    • Intestinal absorption studies showed 68% resorption of the complex versus 56% for indometacin within 10 minutes.

    Conclusions:

    • CHINOIN-137, despite lacking a defined crystalline structure, effectively forms an inclusion complex with indometacin and beta-cyclodextrin.
    • The complexation significantly improves indometacin's aqueous solubility and dissolution rate.
    • Enhanced solubility and complexation lead to improved oral bioavailability and intestinal absorption of indometacin in vivo.