Analysis of the initial burst of drug release coupled with polymer surface degradation

Purpose. Local pH effect on the release of a model pH-inert hydrophobic drug coupled with polymer degradation is described at the induction phase of biodegradable polymer erosion for better understanding the nature of initial burst of a drug. Methods. Using a novel approach with time-of-flight secondary ion mass spectrometry, both surface concentration of Ph₃N and degradation kinetics of PLLA are simultaneously and independently determined from a model Ph₃N/PLLA (20:80 wt%) blend matrix (t ≈ 0.4 μm on 1.0 cm²). In vitro hydrolysis of the model blend matrix is investigated for short-term periods (<24 h) at physiologic pH and temperature and compared to basic pH. Results. The rate of PLLA degradation is accelerated by a factor of ∼3 when using basic pH in vitro, but the rate of Ph₃N accumulation at the surface is accelerated by a factor of ∼6. Conclusions. A new quantitative method has been developed to examine the earliest stages of polymer degradation and drug release. It was applied to a model system that could not be examined by traditional in vitro methods. For the model system studied the release of a low molecular weight hydrophobic drug at the induction phase of polymer erosion is related to but not singularly dependent on degradation kinetics.