A GENERIC PROTEIN DELIVERY SYSTEM BASED ON OSMOTICALLY RUPTURABLE MONOLITHS

The use of osmotic excipients to facilitate delivery of low dose protein drugs from nondegradable polymers was examined. The devices consist of particles of intimately mixed sodium chloride and a protein dispersed in an ethylene vinylacetate (EVA) polymer of 40% vinylacetate content. Protein and NaCl release results from osmotically induced membrane rupture of encapsulated particles subsequent to water imbibition. Using bovine serum albumin (BSA) as a model, the protein mass fraction in the particles was varied from 0.025 to 0.20. A critical value of protein mass fraction in the particle is defined, below which the cumulative mass fraction release rate of NaCl and protein are identical and above which the protein cumulative mass fraction release rate becomes slower than that of NaCl. This limit corresponds to protein saturation in the concentrated salt solution within the particle polymer surrounded capsules. Below this saturation limit, delivery profiles are protein-independent. Protein independence was demonstrated with otherwise identical monoliths containing either BSA, lysozyme or epidermal growth factor.