Preparation and characterization of niosomal gel for iontophoresis mediated transdermal delivery of isosorbide dinitrate.

The purpose of the present study was to improve the bioavailability of isosorbide dinitrate (ISDN) through transdermal route by using cationic niosomal gel as a carrier with anodic iontophoresis. ISDN-loaded cationic niosomes prepared by thin film hydration technique had an average diameter of 262 ± 6.92 nm, polydispersity index of 0.217 ± 0.02, zeta potential of +25.4 ± 0.12, and entrapment efficiency of 68.16 ± 1.14%. The prepared niosomes were incorporated in minimum quantity of carbopol gel which exhibited thixotropic behavior suitable for transdermal application. While free drug was found to degrade upon application of current, interestingly, it was a found that niosomes offered protection to ISDN from degradation during the iontophoresis. The in vitro permeation studies with different current densities showed increase in transdermal flux and decrease in lag time by 11.15- and 2.42-fold (0.5 mA/cm(2)), 12.66- and 2.58-fold (1.0 mA/cm(2)), and 14.46- and 3.75-fold (1.5 mA/cm(2)), respectively, as compared to passive diffusion of free drug. The study confirms the synergistic effect of niosomes and iontophoresis in improving the transdermal permeation profile of ISDN. The enhanced permeation by iontophoresis was investigated by scanning electron microscopy and it was observed that "latent shunt" around the hair follicles became activated and their pore size also increased upon increasing the current densities. Finally, in vivo skin permeation studies demonstrated 2.47 times increased in transdermal bioavailability of ISDN using niosomes in comparison to free drug. The study confirmed that both niosomes and iontophoresis enhance transdermal permeation by two different mechanisms and combination of both has synergistic effect that resulted in higher transdermal flux of ISDN.