Solute and water transport in polymeric, swelling-controlled release systems

Christopher Shawn Brazel, Purdue University

Abstract

Water and solute transport in polymeric matrices was investigated to determine the effects of polymer morphology and composition and solute properties on transport behavior. Two crosslinked polymer systems, poly(2-hydroxyethyl methacrylate-co-methyl methacrylate), P(HEMA-co-MMA), and poly(vinyl alcohol), PVA, were used in sorption and drug release experiments. P(HEMA-co-MMA) samples were prepared containing from 0 to 100 mol % HEMA, with crosslinking ratios ranging from 0.005 to 0.10 mol/mol. PVA networks were formed from linear chains with average molecular weights ranging from 15,000 to 48,000, and having 85 or 99% degrees of acetate group hydrolysis. Rates of swelling, water diffusion coefficients and a dimensionless parameter, the Diffusional Deborah number, De, were used to characterize water uptake processes. Drug release rates and diffusion coefficients, as compared to the drug diffusion coefficient in free solution, and the Swelling Interface number, Sw, were used to characterize solute transport relative to water uptake. The swelling rates correlated well with the crosslinked polymer network mesh sizes, with the slowest rate of water uptake occurring in P(HEMA-co-MMA) samples containing large quantities of the hydrophobic moiety, MMA. The crosslinking ratio had a sizable effect on water uptake in crosslinked PVA, but not in P(HEMA-co-MMA) samples. From swelling experiments, six polymer systems exhibiting a range of transport behavior were selected for further investigation. Drug release experiments were conducted using each of these six polymer systems, with eight model solutes: theophylline, triamterene, oxprenolol HCl, buflomedil HCl, vitamin B$\sb{12},$ dextran, inulin and myoglobin. Drugs were imbedded into the samples by either equilibrium partitioning or loading during the polymerization reaction. Release rates decreased with increasing solute molecular weight, with a molecular weight cut-off, beyond which drug release was greatly hindered by the hydrogel mesh, noted for each polymer. Characteristic polymer relaxation times, and front velocities were determined to be functions of polymer composition, with higher front velocities observed for hydrophilic materials. To gain an understanding of how polymer morphology and solute properties affected transport behavior, the calculated values of De and Sw were correlated to a diffusional exponent, n, indicative of the transport process. A mathematical model of the solvent and solute diffusion processes was used to determine theoretical water uptake and solute release profiles.

Degree

Ph.D.

Advisors

Peppas, Purdue University.

Subject Area

Pharmacology|Polymers|Chemical engineering|Pharmaceuticals

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