SOLUTE AND PENETRANT DIFFUSION IN SWELLABLE POLYMERS (DRUG RELEASE, 2-HYDROXYETHYL METHACRYLATE, N-VINYLPYRROLIDONE COPOLYMERS)
Abstract
A mathematical model was developed to describe diffusion of a penetrant and a solute in a swellable polymer slab. The model was applied to the case of a hydrophilic polymer loaded with a soluble drug in which the penetrant (water) is sorbed and solute (drug) is desorbed. The model allows the incorporation of any appropriate form of the diffusion coefficients; an exponential dependence on penetrant concentration was chosen for demonstration purposes and shown to be adequate for description of the systems studied. Dimensional changes in the sample are predicted by allowing each spatial increment to expand according to the amount of penetrant sorbed. During the initial period of release, the swelling is restricted to one dimension by the glassy core of the sample. At a later point in the process, the center of the sample has sorbed enough penetrant to plasticize it and the sample relaxes to an isotropically swollen state; swelling is thereafter three dimensional. Experimental verification of the model was conducted using copolymers of 2-hydroxyethyl methacrylate (HEMA) and N-vinylpyrrolidone (NVP). The monomers were bulk polymerized in polyethylene vials with benzoyl peroxide initiator and lathe cut into thin disks. Monomer ratios employed were 3:1, 1:1, and 1:3 (volume basis), corresponding to mole fractions of HEMA of 0.707, 0.446, and 0.211. Swelling behavior of the samples was observed in water at 37(DEGREES)C and 0(DEGREES)C. Drug-containing samples were prepared and drug release from these samples into water was followed by monitoring the UV absorption of the release medium. The concentration dependence of the diffusivity of water, and two model solutes, sodium trifluoroacetate and sodium heptafluorobutyrate, in the gels was studied using the pulsed-gradient spin echo NMR technique. The diffusivities measured by this technique followed the concentration dependence predicted by the free volume theory, and it was shown that the simple exponential dependence used in the model was an adequate approximation of this behavior in the case of the transient diffusion experiment. Drug release experiments were also performed with compressed tablets in order to investigate the effect of porosity on swellable drug release systems.
Degree
Ph.D.
Subject Area
Chemical engineering|Pharmaceuticals
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