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Cholesterol gallstone dissolution rate accelerators I: Exploratory investigations

K H Kwan, W I Higuchi, A M Molokhia

    Journal of Pharmaceutical Sciences
    |August 1, 1977
    PubMed
    Summary
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    Researchers investigated compounds to accelerate cholesterol gallstone dissolution. Amines and steroidal amines effectively increased dissolution rates, approaching diffusion-controlled levels, unlike surfactants.

    Area of Science:

    • Biochemistry
    • Pharmacology
    • Materials Science

    Background:

    • Cholesterol gallstones are a common ailment, and their dissolution is often limited by slow kinetics.
    • Previous studies indicated cholesterol dissolution is interfacial resistance controlled, significantly slower than diffusion-controlled rates.

    Purpose of the Study:

    • To identify and evaluate compounds that can act as accelerators for cholesterol gallstone dissolution.
    • To determine the effect of various chemical agents on the dissolution rates of cholesterol monohydrate in synthetic bile.

    Main Methods:

    • Cholesterol monohydrate pellets were used to measure dissolution rates in synthetic bile.
    • Various compounds, including amines and surfactants, were tested at different concentrations.
    • Dissolution rates were compared to diffusion-controlled rates and rates in the absence of accelerators.

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    Main Results:

    • Primary, secondary, tertiary amines, and quaternary ammonium compounds significantly accelerated cholesterol dissolution.
    • Steroidal amines demonstrated notable activity as dissolution accelerators.
    • Anionic and nonionic surfactants showed minimal or inhibitory effects on cholesterol dissolution.
    • High concentrations or sufficient alkyl chain lengths of effective accelerators led to rates approaching diffusion control.

    Conclusions:

    • Amines and steroidal amines are promising candidates for cholesterol gallstone dissolution accelerators.
    • The mechanism of acceleration appears to shift dissolution kinetics towards diffusion control.
    • Further research into these amine compounds could lead to improved therapeutic strategies for gallstones.