Zero-order controlled-release polymer matrices for micro- and macromolecules.

Theoretical and experimental analyses demonstrate that a hemispheric polymer-drug matrix laminated with an impermeable coating, except for an exposed cavity in the center face, can be used to achieve zero-order release kinetics. Hemispheric systems for low molecular weight drugs were prepared by heating and compressing polyethylene and drug (sodium salicylate) in a brass mold. Hemispheric systems for high molecular weight drugs were prepared by casting ethylene-vinyl acetate copolymer and protein in a hemispheric mold at -80 degrees, followed by a two-step drying procedure (-20 and 20 degrees). In both systems, cavities were made in the center face of the hemispheres and the remainder of the matrices coated with an impermeable material. Zero-order release for 60 days at a rate of 0.5 mg/day was achieved from polymer matrices containing bovine serum albumin (mol. wt. 68,000).