Compositions, devices, methods of manufacture, and methods of delivery of a therapeutic substance across a surface of an eyeball via iontophoresis including a therapeutic media reservoir and a buffer system within an iontophoretic chamber. When energized, an electrode provides an electromotive force that transfers a dosage of the therapeutic substance from the iontophoretic chamber across the surface of the eyeball. The buffering system includes a buffer media and at least one buffer element, or agent that regulates pH during iontophoretic transfer of the therapeutic substance. The buffer media includes at least one of a foam, a gel (solid or liquid), a membrane, and a plurality of multiparticulates. The buffer media can be included within the iontophoretic chamber, together with the therapeutic media reservoir, in various arrangements including one or more layers and one or more concentric cylinders.
