Needle-free buccal anesthesia using iontophoresis and amino amide salts combined in a mucoadhesive formulation

Iontophoresis of a hydrogel containing the combination of prilocaine HCl and lidocaine HCl at pH 7.0 enhances the permeation and retention of both anesthetics across porcine esophageal mucosa. [Display omitted] •Combining prilocaine and lidocaine salts affected their distribution coefficients between a gel formulation and a porcine mucosa.•Iontophoresis enhanced 12-fold the permeation of prilocaine hydrochloride through the mucosa when combined with lidocaine hydrochloride at pH 7.•Iontophoresis did not increase lidocaine hydrochloride permeation through the mucosa, however, it did increase lidocaine salt accumulation in there.•Buccal iontophoresis may be a strategy for the replacement of the painful injections of anesthetics. Iontophoresis is a strategy to increase the penetration of drugs through biological membranes; however, its use has been underexplored in mucosa. The aim of this work was to investigate the influence of iontophoresis in the mucosal penetration of prilocaine hydrochloride (PCL) and lidocaine hydrochloride (LCL), which are largely used in dentistry as local anesthetics, when combined in the same formulation. Semisolid hydrogels containing these drugs either alone or in combination were developed at two different pHs (7.0 and 5.8) and presented adequate mechanical and mucoadhesive properties for buccal administration. The distribution coefficients between the mucosa and the formulations (Dm/f) and the in vitro mucosa permeation and retention rates were evaluated for both PCL and LCL. At pH 7.0, the combination of the drugs decreased the Dm/f of PCL by approximately 3-fold but did not change the Dm/f of LCL; iontophoresis increased the permeation rate of PCL by 12-fold and did not significantly change LCL flux compared with the passive permeation rate of the combined drugs. Combining the drugs also resulted in an increase in both PCL (86-fold) and LCL (12-fold) accumulation in the mucosa after iontophoresis at pH 7.0 compared with iontophoresis of the isolated drugs. Therefore, applying iontophoresis to a semisolid formulation of this drug combination at pH 7.0 can serve as a needle-free strategy to speed the onset and prolong the duration of buccal anesthesia.