A GENERIC PROTEIN DELIVERY SYSTEM BASED ON OSMOTICALLY RUPTURABLE MONOLITHS

The use of osmotic excipients to facilitate delivery of low dose prote in drugs from nondegradable polymers was examined. The devices consist of particles of intimately mixed sodium chloride and a protein disper sed in an ethylene vinylacetate (EVA) polymer of 40% vinylacetate cont ent. Protein and NaCl release results from osmotically induced membran e rupture of encapsulated particles subsequent to water imbibition. Us ing bovine serum albumin (BSA) as a model, the protein mass fraction i n the particles was varied from 0.025 to 0.20. A critical value of pro tein mass fraction in the particle is defined, below which the cumulat ive mass fraction release rate of NaCl and protein are identical and a bove which the protein cumulative mass fraction release rate becomes s lower than that of NaCl. This limit corresponds to protein saturation in the concentrated salt solution within the particle polymer surround ed capsules. Below this saturation limit, delivery profiles are protei n-independent. Protein independence was demonstrated with otherwise id entical monoliths containing either BSA, lysozyme or epidermal growth factor.