CONTROLLED MACROMOLECULE RELEASE FROM POLY(PHOSPHAZENE) MATRICES

Hydrolytically unstable poly(phosphazene) PPHOS matrices with 50% ethy l glycinato/50% p-methylphenoxy substitution were investigated as vehi cles for the controlled release of macromolecules. Specifically, the e ffects of matrix pH environment and macromolecule loading were studied . C-14-labeled inulin was incorporated into matrices by a solvent cast ing technique at 1, 10 and 40% loadings (w/w). Degradation and release studies were performed at 37 degrees C at pH 2.0, 7.4 and 10.0. The P PHOS polymer degraded relatively slowly in neutral and basic solutions (pH 7.0 and pH 10.0). In contrast, significantly (p < 0.01) higher le vels of degradation were seen in acidic solutions (pH 2.0) after 35 da ys. The presence of the hydrophilic macromolecule inulin in the polyme r matrix resulted in increased degradation of PPHOS with time. Inulin release, like polymer degradation, was highest at pH 2.0 followed by p H 10.0 and 7.4. Inulin release appeared to be dependent on polymer deg radation and inulin diffusion. High inulin loading increased the level s of initial drug burst release and resulted in higher levels of ultim ate drug release as measured at 25 days. Environmental scanning electr on microscopy (ESEM) demonstrated smooth surfaces on matrices without drug, rough and granular surfaces on matrices loaded with inulin befor e release, and surfaces possessing micropores and macropores after inu lin loading and release. PPHOS polymers can predictably release macrom olecules such as inulin. Release can be modulated through changes in p H environment and drug loading.