A simultaneous transport‐reaction model for controlled drug delivery from catalyzed bioerodible polymer matrices

Abstract

A simultaneous diffusion-reaction model is presented for the analysis of the kinetics of a chemically eroding poly (orthoester) matrix incorporated with a bioactive agent and with a catalyst to promote the erosion. Simulation results are consistent with experimentally observed hollow residuals and provide a basis for analyzing various design options. A. G. THOMBRE SCOPEChemically eroding polymer systems constitute a potentially important class of controlled drug delivery devices since they obviate the need for surgical removal after the delivery is complete. Mathematical modeling of these systems is complex due to the variety of physicochemical processes occurring when the device is exposed to an aqueous environment. In the present study, a transport-reaction model is developed for a poly (orthoesterkbased controlled drug delivery system. Mathematical models that include both transport and chemical kinetics have been extensively applied to the modeling of gas-solid reactions which occur in a variety of chemical process industries. The major applications are found in extractive metallurgy, coal gasification and combustion, and catalyst manufacture. The application of these models to drug delivery systems is relatively new (Korsmeyer and Peppas, 1983;Thombre and Himmelstein, 1983).Numerical simulations using the model developed here lead to quantitative description of the physical processes and their interactions that govern the kinetics of release of the active agent. Also, the model permits the assessment of the relative contributions of various factors to the overall delivery process. Many of the processes under consideration in this study, in particular the use of diffusion-reaction equation sets to develop mathematical models, are applicable to a wide variety of situations involving solid phase reacting systems. CONCLUSIONS AND SIGNIFICANCEIn this study a simultaneous transport-reaction model has been proposed which enables an analysis of the proesses leading to the release of a bioactive agent from a poly (orthoester) matrix. The polymer matrix is subjected to catalytically induced chemical erosion by incorporating an acid anhydride in the matrix. This feature leads to a versatile device for the purpose of administering a drug at a controlled rate. Numerical simulations using the proposed model indicate that the performance of the delivery device, judged by the rate of release of the active agent and the extent of hydrolysis of the poly (orthoester), can be controlled by suitable design of the device. sponsible for the release kinetics of the active agent. The changes in the matrix properties correspond to the extent of hydrolysis of the polymer. The varying matrix properties are reflected in the varying diffusion coefficients of the species involved in the degradation process as well as that of the active agent. The amount of acid anhydride incorported in the matrix, and to some extent the partition coefficient of water relative to the matrix, are under the control of the device designer. The model indicate...

Effect of drug type on the degradation rate of PLGA matrices

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