Non-invasive drug delivery systems useful for the absorption of therapeutically active agents through the epithelial membrane are described. The non-invasive drug delivery system delivers a therapeutic active agent with an ionizable, or ionized, metal, transition metal or metal-containing vehicle. The non-invasive drug delivery system may also have a pH adjustable vehicle which facilitates the absorption of the therapeutic agents by altering the pH of the non-invasive drug delivery system at the site of administration. Also disclosed is a method for the pH &ldquo；sweeping&rdquo； of the administered therapeutic active agent to provide a consistent and reproducible absorption of the active agent. Certain formulations utilize low doses of active agents without altering the active agents from their current or previous form.
