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Analysis of the Initial Burst of Drug Release Coupled with Polymer Surface Degradation

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Abstract

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.

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Correspondence to Joseph A. Gardella Jr..

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Lee, JW., Gardella, J.A., Hicks, W. et al. Analysis of the Initial Burst of Drug Release Coupled with Polymer Surface Degradation. Pharm Res 20, 149–152 (2003). https://doi.org/10.1023/A:1022202632685

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