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Analysis of the initial burst of drug release coupled with polymer surface degradation
Joo-Woon Lee1, Joseph A Gardella, Wesley Hicks
1Department of Chemistry, University at Buffalo, The State University of New York, Buffalo, New York 14260-3000, USA.
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 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.
Results:
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.
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.