Compositions, devices, method 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 and 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 on 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 multi-particulates. The buffer media can be included within the iontophoretic chamber, together with the therapeutic media reservoir, in various arrangements including on or more layers and one or more concentric cylinders.