1. Results and Discussion (Part 3) Dan Duffield Rick Pelletier 2-14-2006

2. Previous Equations  Equations 1 through 9 have several limitations and do not apply- At low loadings (<15%), pore space may not be interconnected. For macromolecules whose solubility is less than 250 mg/mL.

3. F factor and Porosity  The relation between the F factor and the porosity in Equation 9 is empirical.  This may not be useful outside its known range of validity (0.15< <0.35)

4. Simplification of Diffusion Equations  The diffusion equations used in this study are simplifications of more complex processes.  The factor F must take into account matrix pore geometric factors contributing to decreases in diffusion rates such as Pore “Tortuosity” Dead-end Pores Constrictions between pores  Understanding of these factors will be important in further developing macromolecular delivery systems.

5. Release Rates  In vitro and in vivo release rates of macromolecules from identical EVAc slabs are identical.  Constant release rates are attainable from EVAc systems with appropriate geometric design.

6. Use of Present Study  Helps to explain why macromolecules can slowly permeate through normally impermeable polymers.  Data should be useful in the design of release vehicles for- Polypeptides Polysaccharides Bioactive agents

7. Use of Present Study (cont.)  These substances often possess very short in vivo life times and conventional dosage forms can not be used to deliver these drugs.  The methodology developed here may be of value in the design of systems for long- term delivery of macromolecules.

8. Questions ?