A novel model and experimental analysis of hydrophilic and hydrophobic agent release from biodegradable polymers

Abstract

Many factors affect the rate of drug release from biodegradable polymers. Here, we focus on investigating the effect of drug type on the degradation of P(DL)LGA 53/47 films and their ultimate release profiles. A freely water-soluble drug (metoclopramide monohydrochloride) exhibited an initial burst, whereas a water-insoluble drug (paclitaxel) exhibited an initial latent period with very little drug release. The onset of the second-stage release of the hydrophobic drug was delayed as compared with the hydrophilic drug. Overall, complete release of metoclopramide monohydrochloride was achieved much earlier than paclitaxel. In addition, the hydrophobic drug exhibited an extra stage of release when compared with the two-stage release for the hydrophilic drug. A novel model was developed to describe the underlying drug release mechanisms and kinetics. The model postulated that the total fraction of drug release from bulk-degrading polymer is a summation of three mechanisms: burst release, relaxation induced/drug-dissolution controlled release, and diffusional release. All the three steps are important for hydrophobic drugs. However, for hydrophilic drugs, burst and diffusional release steps are sufficient to account for the whole release process. The proposed model showed very good match with the experimental data.