Ionizable drugs and pH oscillators: Buffering effects

Gauri P. Misra, Ronald A. Siegel

Research output: Contribution to journalArticlepeer-review

17 Scopus citations

Abstract

It has been proposed that chemical pH oscillators may form a basis for periodic, pulsed drug delivery of weak acids and bases across lipophilic membranes. However, drugs have been shown to interfere with the ability of the chemical systems to oscillate, and rhythmic delivery of drugs by this means has been demonstrated only under constrained circumstances. Herein, we provide evidence that low concentrations of acidic drugs can attenuate and ultimately quench chemical pH oscillators, by a simple buffering mechanism. A model system consisting of the bromate-sulfite-marble pH oscillator in a continuous stirred tank reactor is used, along with acidic drugs of varying concentration and acid dissociation constant, pKD. A published kinetic model for this oscillator is modified to account for the presence of acidic drug, and the results of this model are in qualitative agreement with the experimental results.

Original languageEnglish (US)
Pages (from-to)2003-2015
Number of pages13
JournalJournal of Pharmaceutical Sciences
Volume91
Issue number9
DOIs
StatePublished - Sep 1 2002

Bibliographical note

Funding Information:
This work was supported by NSF Grant CHE‐9996223. We thank Jeffrey D. Zahn for initial assistance in the modeling work, Anya Grosberg for assistance in preparing figures, and David Grant, Thomas Hoye, Glen Frerichs, Richard Field, Hans Othmer, Minchul Kang, and Anish Dhanarajan for helpful discussions. A referee is acknowledged for the suggestion that effects of concentration of added H 2 SO 4 be examined.

Keywords

  • Buffering
  • Chemical oscillator
  • Drug delivery
  • Marble
  • PH

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