Temporally Controlled Drug Delivery Systems: Coupling of pH Oscillators with Membrane Diffusion

Giannos, Steven A.; Dinh, Steven M.; Berner, Bret

doi:10.1002/jps.2600840505

Cited by 37 publications

(44 citation statements)

References 17 publications

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“…Consistent with results reported by Giannos et al, 14 we find that oscillations are affected by drugs via a buffering mechanism which is a consequence of the same acid/base equilibrium that modulates drug permeability through lipophilic membranes. The pattern of buffer effect depends on drug concentration and acidity (pK D ), as demonstrated both by experiment and by theoretical considerations.…”

Section: Discussionsupporting

confidence: 94%

“…Because pH oscillators tend to be nonlinear in character, there are no immediately obvious guidelines allowing one to predict precise limits without performing analyses similar to those presented here. Nevertheless, we believe that the present investigation provides a valid explanation for the quenching effect of drug on pH oscillators that was observed by Giannos et al 14 The modeling work was intended to provide a theoretical correlation with the experiments. The correspondence between the theory and experiment should be regarded as only qualitative, because there are some quantitative discrepancies.…”

Section: Discussionmentioning

confidence: 66%

“…In the semibatch configuration described by Giannos et al, 14 reactants are steadily added to the reaction but products are not removed, and volume steadily increases. Although the semibatch configuration is probably the most realistic for the design of drug delivery systems involving oscillating chemical reactions, it is problematic for basic studies because the chemical conditions are always changing due to accumulation of products and change of volume.…”

Section: Experimental Section Backgroundmentioning

confidence: 99%

“…12 Recently, we have provided evidence for the feasibility of an enzyme/hydrogel system which, due to a negative chemomechanical feedback instability, swells and deswells regularly in the presence of a constant level of glucose, thus providing the basis for periodically modulated drug release. 13 Giannos et al 14 proposed a novel scheme for periodic drug delivery based on the effect of pH on the permeability of acidic and basic drugs through lipophilic membranes. By including ingredients of a chemical pH oscillator in the drug reservoir, 15 it was predicted that drug flux through such a membrane would be modulated according to the periodic pH swings, as illustrated in Figure 1.…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Ionizable drugs and pH oscillators: Buffering effects

Misra

Siegel

2002

Journal of Pharmaceutical Sciences

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Section: Discussionsupporting

confidence: 94%

Section: Discussionmentioning

confidence: 66%

Section: Experimental Section Backgroundmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Ionizable drugs and pH oscillators: Buffering effects

Misra

Siegel

2002

Journal of Pharmaceutical Sciences

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“…5 A good oscillator with long period and large amplitude is offered here. In this context the advantage of the present system is that the length of the low-pH state relative to that of the high-pH state within a cycle can be varied by using different amounts of marble.…”

Section: Resultsmentioning

confidence: 99%

pH Oscillations in the Bromate−Sulfite−Marble Semibatch and Flow Systems

Rábai

Hanazaki

1996

J. Phys. Chem.

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A self-accelerating oxidation of an unbuffered aqueous sodium sulfite-hydrogen sulfite solution by sodium bromate and a selective removal of the hydrogen ion by solid marble chips from the reaction mixture have been used to construct an oscillatory system. The system exhibits large-amplitude oscillations between pH 3.5 and 7.5 at 25.0°C in a continuous-flow stirred tank reactor and in a semibatch configuration. The shape, the periodic time (from 10 min to 2 h), and the region of oscillations can be controlled by using different amounts and grade size of marble. A simple reaction scheme, consisting of the protonation equilibria of SO 3 2-and HSO 3 -, the oxidation of HSO 3 -and H 2 SO 3 by BrO 3 -, and a removal of H + by the CaCO 3 in marble in the form of HCO 3 -has successfully been used to simulate the observed dynamical behavior.

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Drug Delivery Systems

Kost¹,

Lapidot²

2002

Encyclopedia of Smart Materials

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The basic approach that drug concentration–effect relationships are significantly invariant as a function of time in humans has led to the development of constant‐rate drug delivery systems. Nevertheless, there are a number of clinical situations where such an approach may not be sufficient. These include the delivery of insulin for patients who have diabetes mellitus, antiarrhythmics for patients who have heart rhythm disorders, gastric acid inhibitors for ulcer control, nitrates for patients who have angina pectoris, as well as selective β‐blockade, birth control, general hormone replacement, immunization, and cancer chemotherapy.In recent years, several research groups have been developing responsive systems that could more closely resemble the normal physiological process where the amount of drug released can be effected according to physiological needs. Responsive polymeric delivery systems can be classified as open or closed‐loop systems. Open‐loop control systems are those where information about the controlled variable is not automatically used to adjust the system inputs to compensate for the change in the process variables. In closed‐loop control systems, the controlled variable is detected, and as a result the system output is adjusted accordingly. In the controlled drug delivery field, open‐loop systems are known as pulsatile or externally regulated, and closed‐loop systems as self‐regulated. The externally controlled devices apply external triggers such as magnetic, ultrasonic, thermal, or electric irradiation for pulsatile delivery. In self‐regulated devices, the release rate is controlled by feedback information without any external intervention. Self‐regulated systems use several approaches as rate control mechanisms: pH‐sensitive polymers, enzyme–substrate reactions, pH‐sensitive drug solubility, competitive binding, antibody interactions, and metal concentration‐dependent hydrolysis.

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Temporally Controlled Drug Delivery Systems: Coupling of pH Oscillators with Membrane Diffusion

Cited by 37 publications

References 17 publications

Ionizable drugs and pH oscillators: Buffering effects

Ionizable drugs and pH oscillators: Buffering effects

pH Oscillations in the Bromate−Sulfite−Marble Semibatch and Flow Systems

Drug Delivery Systems

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