Results and Discussion Loren Connell Eric Skibbe

Microscopy Observations EVAc (ethylene-vinyl acetate copolymer) films cast without proteins appear as non-porous sheets Slabs cast with proteins and sectioned before release show polymer or protein areas Slabs cast with proteins and released completely appear as porous films

Creation of Pores The pores observed were as large as 100um –The structures were confirmed with differential interference microscopy Pure EVAc is impermeable to macromolecules Molecules in the matrix dissolve when water penetrates the matrix As the particles dissolve, they create pores through which they can diffuse to the surface Narrow passages interconnecting the pores were also observed

Pore Structure Observations Changes in pore structure over time were investigated Observations: –Pore structure changes minimally with time –There was no receding interface between the dissolved and dispersed drug after 16 to 40 hours –No undissolved drug left after 40 hours (30% release) –This is most likely due to the high solubility of the proteins used

Model Development Assumptions Drug diffusion through pores is rate- limiting step Effect of concentration dependence on drug diffusion is not significant No diffusion through polymer backbone Pores are interconnected, porosity uniform, pore size changes minimally with time

Model Development Assumptions Continued Initial drug distribution is uniform No boundary layer effects Infinite sink conditions Minimal effects due to osmosis or charge interaction of the drug with polymer Release only from one face of slab (other faces coated with impermeable wax)

Modeling of Release Fick’s second Law Boundary Conditions Initial Condition