Controlled release systems kinetics

Bonny, J. and Leuenberger, H., Matrix type controlled release systems I. Effect of percolation on drug dissolution kinetics, Pharmaceutica Acta Helvetiae, Vol. 66, No. 5-6, 1991, pp. 160—164. 

In 1991, Bonny and Leuenberger [40] explained the changes in dissolution kinetics of a matrix controlled-release system over the whole range of drug loadings on the basis of percolation theory. For this purpose, the tablet was considered a disordered system whose particles are distributed at random. These authors derived a model for the estimation of the drug percolation thresholds from the diffusion behavior. 

In summary, the studies reported In this review provide 2 Important demonstrations (1) that In vitro release kinetics of macromolecules such as inulln from ethylene-vinyl acetate copolymer matrices are Identical to their In vivo release kinetics, and (2) that zero-order release for macromolecules can be achieved for over 60 days using a hemisphere design. Further experimentation in these areas should provide Information that will be useful In the eventual design of controlled release systems for Insulin and other important bloactlve macromolecules. 

Lee, P. L, 1988, Synthetic hydrogels for drag delivery Preparation, characterization, and release kinetics, in Controlled Release Systems Fabrication Technology, Vol. II (D. S. T. Hsieh, ed.), CRC Press, Boca Raton, Florida, pp. 61-82. 

The release of 5-fluorouracil from the [EMCF] copolymers follows a different mechanism than the release of 5-FU from a monolithic dispersion in poly(caprolactone). The copolymers consistently exhibit zero-order kinetics while the [FUPC] systems never show this pattern. In addition, much higher levels of the 5-FU can be incorporated into the polymeric system than into the monolithic dispersion system. In the present case, this was 45+% compared to less than 25%. For therapeutic use, the zero-order kinetics would offer the additional advantage of a completely controlled dose rate that could be maintained constant for long periods of time. The exact release rate can be controlled through the concentration of the drug monomer in the copolymer and the nature of the comonomer(s). This combination of properties can not be readily obtained in any other system without the use of complex membranes and the like. In short, the polymeric drug approach does offer many distinct advantages over the usual controlled release systems and should prove to be the more desirable system for use in medication. 

Controlled release systems can be obtained by loading HEMA hydrogels with an antibiotic dmg, either by soaking preformed polymers in methronidasole solutions or by direct polymerization of monomer/dmg mixtures. Also the release of methronidasole in water obeyed diffusive type kinetics, albeit at a slower rate than water and it was completed within 10 hours. 

A different but very important area of chemical engineering in the life sciences involves the design and manufacture of health care systems for diagnostic or therapeutic purposes. Consider the example of controlled release drugs or dermal penetration drugs. Here the emphasis is on the system rather than on the compound. The design of these systems requires an understanding of reactions, kinetics, fluid mechanics, and membrane systems. 

The regulation of drug input into the body is the core tenet of controlled release drug delivery systems. With advances in engineering and material sciences, controlled release delivery systems are able to mimic multiple kinetic types of input, ranging from instantaneous to complex kinetic order. In this section three of the most common input functions found in controlled release drug delivery systems will be discussed— instantaneous, zero order, and first order. 

Factors analogous to those affecting gut absorption also can affect drug distribution and excretion. Any transporters or metabolizing enzymes can be taxed to capacity—which clearly would make the kinetic process nonlinear (see Linear versus Nonlinear Pharmacokinetics ). In order to have linear pharmacokinetics, all components (distribution, metabolism, filtration, active secretion, and active reabsorption) must be reasonably approximated by first-order kinetics for the valid design of controlled release delivery systems. 

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