Transdermal iontophoresis of insulin. II. Physicochemical considerations

Int J Pharm. 2003 Mar 26;254(2):271-80. doi: 10.1016/s0378-5173(03)00034-6.

Abstract

Transdermal iontophoresis is one of the potential enhancement strategies for the delivery of large and charged molecules. Insulin, a polypeptide of 6 kDa was used as a model for large peptides to understand the influence of peptide concentration, NaCl concentration, buffer type and its concentration on the transport efficiency of iontophoresis. Maximum enhancement was found at 3 mg/ml (75 IU/ml). The permeation of insulin was found to increase up to 0.05 M NaCl and decreased at higher concentrations of NaCl. The glucose permeation studies showed that permeation of insulin increased in the presence of NaCl due to ion induced convective flow. The flux enhancement of insulin in the presence of phthalate buffer was higher in comparison to citrate buffer, but the enhancement in these two buffers was the same in the presence of 0.05 M NaCl, which was also supported by a similar trend in conductivity values. However, the solution conductivity values did not reflect the influence of co-ions and counter ions on the transport of large peptides across the skin. Overall the findings revealed that the transport efficiency of large peptides like insulin may be improved by the optimisation of competing ions in solution.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Cutaneous
  • Animals
  • Anions
  • Biological Transport
  • Buffers
  • Cations
  • Hydrogen-Ion Concentration
  • In Vitro Techniques
  • Insulin / administration & dosage*
  • Insulin / chemistry
  • Insulin / pharmacokinetics*
  • Iontophoresis / methods
  • Male
  • Osmolar Concentration
  • Rats
  • Rats, Sprague-Dawley
  • Skin / metabolism
  • Skin Absorption
  • Sodium Chloride

Substances

  • Anions
  • Buffers
  • Cations
  • Insulin
  • Sodium Chloride