Glucose transport through human skin can be facilitated by electroosmotic flow that results from the application of an electric current across the skin (iontophoresis). A series of studies on human volunteers examined how formulation factors (buffer type, pH, ionic strength, and buffer concentration) affect the amount of glucose extracted from interstitial fluid through the skin. Sampling cells were placed on subjects' forearms and a current of 0.25 mA/cm(2) was passed across the skin for 5 h. Samples were collected every 20 min and analyzed for glucose concentration. Two methods were used. In one method, subjects ingested glucose and one formulation was tested in each pair of sampling cells for the study duration. The ratio of transdermal glucose flux to blood glucose was determined and compared across formulations. In another method, subjects fasted through the study, and different formulations were sequentially tested in each sampling cell. Citrate was found to give higher flux than bicarbonate or phosphate buffers. Transport increased with increasing pH from 4.5 to 6.5 for citrate buffer and 6.5 to 7.5 for bicarbonate buffer. Increased salt concentration in the formulation decreased transport. Increased phosphate concentration increased transport. These results can be used to optimize electroosmotic transport through the skin.