EFFECT OF POLYMER FOAM MORPHOLOGY AND DENSITY ON KINETICS OF IN-VITROCONTROLLED-RELEASE OF ISONIAZID FROM COMPRESSED FOAM MATRICES

The purpose of this study was to compare the effect of polymer foam mo rphology and density prior to compaction on the kinetics of isoniazid (INH) release from the final high-density extruded matrices. The feasi bility of preparing low density foams of several biopolymers, includin g poly(L-lactide) (PLLA), poly(glycolide) (PGA), poly(DL-lactide-co-gl ycolide) (PLGA), poly(gamma-benzyl-L-glutamate) (PBLG), and poly(propy lene fumarate) (PPF), via a lyophilization technique was investigated. Low-density foams of PLGA, PBLG, and a mixture of PLGA and PPF were s uccessfully fabricated by lyophilization of the frozen polymer solutio ns either in glacial acetic acid or in benzene. The morphology of thes e foams depends on the polymer as well as the solvent used in the fabr ication process. Thus, PLGA produces a capillary structure when lyophi lized from benzene solution and a leaflet structure from glacial aceti c acid, but PBLG yields a leaflet structure from benzene. Matrices wer e prepared by impregnating these foams with aqueous solutions of INH, removing the water by a second lyophilization, and then compressing th e low-density INH containing foams by compaction and high-pressure ext rusion. The resulting nonporous matrices had densities of approximatel y 1.30 g/cm(3). In vitro kinetics were in accord with the Roseman-Higu chi diffusion model and demonstrate that release rates depend on the i nitial foam density, while foam structure has little influence on the release kinetics. (C) 1997 John Wiley & Sons, Inc.