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Randomized controlled trial. The researcher measuring skin pH was blinded to group assignment.To compare the skin surface pH changes associated with iontophoresis. The investigation was designed to address the question of whether significant skin pH changes occur under the cathode on the skin surface when performing iontophoresis and assessed the influence of different electrode-buffering systems intended to stabilize skin pH (surface).Whether buffers are needed to stabilize skin pH during iontophoresis has not been thoroughly addressed in the literature. The effectiveness of immobile resins versus simple phosphate buffers is also unclear.Sixty volunteer subjects were administered iontophoresis of normal saline using buffered or nonbuffered electrode systems. Each subject participated in 1 of the 12 doses by electrode conditions (i.e., 5 subjects per group). Surface skin pH was measured before and after iontophoresis with a flat-surface pH electrode in concert with an analog pH meter. The independent variables were electrode type (4 levels) and dosage (3 levels). The dependent variable was the change in skin surface pH.A significant change in skin pH was found only when the treatment dose was 80 mA/minute with a nonbuffered electrode (x = 3.14 +/- 1.09).The skin pH changes that occur during a properly delivered iontophoresis treatment at dosages of 20 and 40 mA/min were small and not significantly different with or without the addition of buffers. Those pH changes associated with 80 mA/min doses were significantly greater when no buffer was employed but were stabilized by each of the buffers used in the study (preloaded immobile resins or simple phosphates added at point of treatment).