Controlled simultaneous iontophoresis of buflomedil hydrochloride and dexamethasone sodium phosphate to the mucosa for oral submucous fibrosis

Int J Pharm. 2021 Sep 25:607:121009. doi: 10.1016/j.ijpharm.2021.121009. Epub 2021 Aug 12.

Abstract

A novel concentric experimental set-up was used to investigate short-duration topical co-iontophoresis of cationic buflomedil hydrochloride (BUF) and anionic dexamethasone phosphate (DEX-P) to the oral mucosa. A constant current of 3.0 mA (0.6 mA/cm2 for BUF and 1.95 mA/cm2 for DEX-P) was applied to porcine esophageal mucosa for 5, 10 and 20 min. Iontophoresis for only 5 min increased total delivery of BUF from 29.8 ± 5.1 nmol/cm2 to 194.3 ± 23.8 nmol/cm2 and DEX-P from 29.4 ± 1.2 nmol/cm2 to 193.3 ± 19.8 nmol/cm2 as compared to passive controls. Quantification of drug between the electrode compartments reported on lateral ion migration. In the absence of current, DEX-P did not migrate laterally; however, iontophoresis for 5 min increased DEX-P delivery >5-fold under the cathodal compartment (its application area) and >8-fold in the adjacent "inter-electrode" area. Similarly, delivery of BUF increased ~6.8-fold under the anodal compartment and ~12.8-fold under the cathode. The results showed that co-iontophoresis enabled the controlled simultaneous delivery of BUF and DEX-P achieving therapeutically relevant concentrations after current application for only 5 min. Short duration topical co-iontophoresis of single or multiple therapeutics to the mucosa increases local bioavailability and presents a patient-friendly treatment for diseases of the oral cavity.

Keywords: Buccal delivery; Buflomedil; Dexamethasone; Fibrosis; Iontophoresis; Topical delivery.

MeSH terms

  • Administration, Cutaneous
  • Animals
  • Dexamethasone / analogs & derivatives
  • Humans
  • Iontophoresis*
  • Mouth Mucosa
  • Oral Submucous Fibrosis*
  • Pyrrolidines
  • Swine

Substances

  • Pyrrolidines
  • dexamethasone 21-phosphate
  • Dexamethasone
  • buflomedil