Bioerodible polyanhydrides as drug‐carrier matrices. I: Characterization, degradation, and release characteristics

Abstract

Polyanhydrides based on a variety of aromatic and aliphatic dicarboxylic acids were developed as bioerodible carrier matrices for controlled delivery applications. The high hydrolytic reactivity of the anhydride linkage provides an intrinsic advantage over other classes of bioerodible polymers in versatility and control of degradation rates. For example, using the poly[bis(p‐carboxyphenoxy) alkane anhydrides] as models, polymers with degradation rates in the range of 10⁻¹ to 10⁻⁴ mg/h/cm² were obtained by changing the alkane from a methyl to a hexyl group. The polymers were characterized by infrared (IR), differential scanning calorimetry, gel permeation chromatography, and scanning electron microscopy (SEM). Near zero‐order degradation kinetics were observed for the hydrophobic polyanhydrides over several months. The drug release profile of the model drug p‐nitroaniline followed closely that of the degradation of injection‐molded poly[bis(p‐carboxyphenoxy) propane anhydride] over a period of more than 8 months. Close correlation of polymer degradation and drug release was also observed in other injection‐molded samples (10% loading), suggesting a release mechanism that was dominantly degradation controlled. Degradation of these polyanhydrides was pH sensitive, being enhanced in high pH, and became more stable in acidic conditions.