The effects of iontophoresis and electroporation on transdermal delivery of buprenorphine from solutions and hydrogels

Abstract

The in-vitro permeation of buprenorphine across skin was investigated to assess the effects of iontophoresis and electroporation on drug permeation from solutions as well as from hydrogels. Iontophoresis (0.3 mA cm−2) increased the buprenorphine permeation from solution by a factor of 14.27 as compared with passive diffusion; the application of electroporation increased the buprenorphine permeation from solutions by a factor of 8.45. The permeation experiments using cellulose membrane and stratum corneum (SC)-stripped skin as permeation barriers suggested that the enhancement with iontophoresis was primarily due to strong electrophoretic drift of buprenorphine molecules, whereas the enhancement seen with electroporation was mainly attributed to the creation of transient aqueous pores in the SC layer. Application of high-voltage pulses followed by iontophoresis resulted in a shorter permeation onset time from both solutions and hydrogels as compared with iontophoresis or electroporation alone. The charge repulsion between buprenorphine and chitosan vehicles as well as the competition effects of counter-ions for carboxymethylcellulose (CMC)-based polymers may account for the different permeation rates under electrical field. This study demonstrates the feasibility of using hydrogels for delivery of buprenorphine under the application of iontophoresis or electroporation, separately or together.