Prediction of microclimate pH in poly(lactic-co-glycolic acid) films

被引：0
|
作者：
Ding, Amy G. [1 ,2 ]
Shenderova, Anna [1 ]
Schwendeman, Steven P. [1 ]
机构：
[1] Department of Pharmaceutical Sciences, University of Michigan, Ann Arbor, MI 48109-1065, United States
[2] ALZA Corporation, Mountain View, CA 94043, United States
来源：
Journal of the American Chemical Society | 2006年 / 128卷 / 16期
关键词：
An equilibrium mathematical model that accurately predicts microclimate pH (μpH) in thin biodegradable polymer films of poly(lactic-co-glycolic acid) (PLGA) is described. μpH kinetics was shown to be primarily a function of: (i) kinetics of water-soluble acid content and composition in the polymer matrix and (ii) polymer/water partition coefficient of water-soluble degradation products (Pi). Polymers were coated on standard pH glass electrodes; and μpH was measured potentiometrically. Water-soluble acid distribution and content in PLGA films were determined by pre-derivatization HPLC. Polymer degradation products partitioned favorably in the polymer phase relative to water (P range: ∼6-100); and P increased with increasing hydrophobicity of the acidic species according to a linear free energy law related to reversed phase HPLC retention time for the corresponding derivatized bromophenacyl esters. The μpH predicted by the model was in excellent agreement with experimental μpH for several PLGAs as a function of time and PLGA lactic/glycolic acid ratio. These data may be useful to slowly release pH-sensitive PLGA-encapsulated bioactive substances and provide a general framework for predicting partitioning behavior of degradation products in biodegradable polymers. © 2006 American Chemical Society;
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页码：5384 / 5390
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