10052
Macromolecules 2004, 37, 10052-10058
Potentiometric Method for Determination of Microclimate pH in Poly(lactic-co-glycolic acid) Films Anna Shenderova,† Amy G. Ding,‡ and Steven P. Schwendeman*,‡ Esperion Division of Pfizer, Ann Arbor, Michigan 48108, and Department of Pharmaceutical Sciences, The University of Michigan, Ann Arbor, Michigan 48109-1065 Received September 2, 2004
ABSTRACT: The acidic microclimate pH (µpH) in poly(lactide-co-glycolide) (PLGA) devices has been identified as a major source of instability of encapsulated proteins and acid labile small molecules. A fast and reliable potentiometric technique for µpH measurement in thin PLGA films was developed and validated. Standard glass pH electrodes were coated with PLGA films, and the zero-current potential was measured with respect to a calomel reference electrode. The measurement was independent of external media pH but responsive to addition to the polymer films buffering salts from lyophilized solutions of various pH values. The contribution of additional diffusion and interfacial potentials in the electrochemical cell due to the presence polymer coating was determined to be roughly e0.2 pH units by two independent measurements and slightly pH dependent. A highly acidic µpH (µpH
