Ionizable drugs and pH oscillators: buffering effects.
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, pK(D). 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.
Misra
Gauri P
GP
Department of Pharmaceutics, University of Minnesota, Twin Cities Campus, Minneapolis, Minnesota 55455, USA. siege017@tc.umn.edu
Siegel
Ronald A
RA
D019342:Acetic Acid / Q000737:chemistry; D000465:Algorithms; D019817:Benzoic Acid / Q000737:chemistry; D002021:Buffers; D002626:Chemistry, Pharmaceutical; D006863:Hydrogen-Ion Concentration; D007477:Ions / Q000737:chemistry; D007700:Kinetics; D008956:Models, Chemical; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D020156:Salicylic Acid / Q000737:chemistry; D012995:Solubility
D002021:Buffers; D007477:Ions; D004364:Pharmaceutical Preparations; D019817:Benzoic Acid; D020156:Salicylic Acid; D019342:Acetic Acid