The purpose of this work was to study the comparative and combination enhancement of an almost ideal transdermal drug through physical and chemical penetration enhancement methods. Tolterodine tartrate loaded invasomes were prepared using soya lecithin, ethanol and three different terpenes viz. limonene, fenchone and anethole. The FT-IR results showed the compatibility of these excipients with the drug. The obtained invasomes were of a sufficiently small vesicle size (1.3μm) with polydispersity index of 0.188. The vesicles were stable with no significant changes in the entrapment efficiency for a period of two months and there was no observed erythema which was proved by skin irritation studies on rabbits. Ex- vivo skin penetration data revealed that the invasome dispersion showed a significantly enhanced penetration of the drug through the skin compared to vesicles without terpenes, ethanolic drug solution and drug solution. Invasome formulation containing limonene showed high penetration because of its lipophilicity and low boiling point. The results of iontophoretic drug transport showed that the permeability of tolterodine tartrate released from invasomes was higher compared with that of free drug proving the additive effect of invasomes and iontophoresis. Hence successful transdermal penetration was obtained in combination with both physical and chemical penetration techniques.
