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Ionizable drugs and pH oscillators: buffering effects.

Gauri P Misra1, Ronald A Siegel

  • 1Department of Pharmaceutics, University of Minnesota, Twin Cities Campus, Minneapolis, Minnesota 55455, USA. siege017@tc.umn.edu

Journal of Pharmaceutical Sciences
|September 5, 2002
PubMed
Summary

Acidic drugs can disrupt chemical pH oscillators, hindering their use for pulsed drug delivery. Even low drug concentrations, acting as buffers, can stop these chemical oscillations.

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Area of Science:

  • Chemical Oscillations
  • Drug Delivery Systems
  • Physical Chemistry

Background:

  • Chemical pH oscillators have been proposed for pulsed drug delivery across lipophilic membranes.
  • However, drug molecules can interfere with oscillator function, limiting practical applications.

Purpose of the Study:

  • To investigate how acidic drugs affect chemical pH oscillators.
  • To understand the mechanism by which drugs interfere with oscillator behavior.

Main Methods:

  • Utilized a bromate-sulfite-marble pH oscillator in a continuous stirred tank reactor.
  • Introduced acidic drugs with varying concentrations and acid dissociation constants (pK(D)).
  • Modified a published kinetic model to incorporate drug effects.

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Main Results:

  • Low concentrations of acidic drugs were found to attenuate and quench the chemical pH oscillators.
  • A simple buffering mechanism was identified as the cause of oscillation disruption.
  • Experimental results showed qualitative agreement with the modified kinetic model.

Conclusions:

  • Acidic drugs, even at low concentrations, can effectively inhibit chemical pH oscillators.
  • The buffering capacity of acidic drugs is a key factor in disrupting oscillatory behavior.
  • The findings suggest limitations for using chemical oscillators in drug delivery systems when acidic drugs are involved.