title: Needle-free buccal anesthesia using iontophoresis and amino amide salts combined in a mucoadhesive formulation.
abstract: 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.
authors.affiliation: University of São Paulo, School of Pharmaceutical Sciences of Ribeirão Preto, Ribeirão, SP, Brazil.
authors.forename: Camila
authors.initials: C
authors.lastname: Cubayachi
authors.affiliation: University of São Paulo, School of Pharmaceutical Sciences of Ribeirão Preto, Ribeirão, SP, Brazil.
authors.forename: Renê Oliveira do
authors.initials: RO
authors.lastname: Couto
authors.affiliation: University of São Paulo, School of Pharmaceutical Sciences of Ribeirão Preto, Ribeirão, SP, Brazil.
authors.forename: Cristiane Masetto
authors.initials: CM
authors.lastname: de Gaitani
authors.affiliation: University of São Paulo, School of Dentistry of Ribeirão Preto, Ribeirão Preto, SP, Brazil.
authors.forename: Vinícius
authors.initials: V
authors.lastname: Pedrazzi
authors.affiliation: University of São Paulo, School of Pharmaceutical Sciences of Ribeirão Preto, Ribeirão, SP, Brazil.
authors.forename: Osvaldo de
authors.initials: Od
authors.lastname: Freitas
authors.affiliation: University of São Paulo, School of Pharmaceutical Sciences of Ribeirão Preto, Ribeirão, SP, Brazil. Electronic address: rvianna@fcfrp.usp.br.
authors.forename: Renata Fonseca Vianna
authors.initials: RF
authors.lastname: Lopez
mesh_terms: D000577:Amides / Q000737:chemistry*; D000758:Anesthesia / Q000379:methods*; D002610:Cheek; D006801:Humans; D007478:Iontophoresis / Q000379:methods*; D009061:Mouth Mucosa / Q000737:chemistry; D012492:Salts
chemical_list: D000577:Amides; D012492:Salts
keywords: Iontophoresis; Lidocaine; Mucoadhesion; Mucosa; Needle-free anesthesia; Prilocaine