Abstract
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. 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 approximately 0.4 microm 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. The rate of PLLA degradation is accelerated by a factor of approximately 3 when using basic pH in vitro, but the rate of Ph3N accumulation at the surface is accelerated by a factor of approximately 6. 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.
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