Utility of nanosized microemulsion for transdermal delivery of tolterodine tartrate: ex-vivo permeation and in-vivo pharmacokinetic studies.

PURPOSE: The aim of this work was to investigate the feasibility of using nanosized microemulsion for transdermal delivery of tolterodine tartrate.

METHODS

The effect of three microemulsions formed by Labrasol: Plurol (3:1), isopropyl myristate and water on the permeation of tolterodine through miniature pig skin was studied in vitro using Franz diffusion cell. For comparison purpose, the effect of different vehicles on the permeation was also studied. Drug pharmacokinetics was studied after transdermal application to human volunteers compared to the commercial oral dosage form using a newly developed LC-MS/MS assay.

RESULTS

The vehicle PEG 400:Phosphate buffer pH 7.4 in the ratio of 1:1 significantly enhanced tolterodine permeation across pig skin. The microemulsion system (ME3) containing the highest amount of water (50%) significantly enhanced permeation with Q(24) of 0.746 mg.cm(-2). In contrast to oral delivery, a sustained activity was observed over a period of 72 h after transdermal application of this microemulsion to human volunteers with significant lower C(max) (1.06 ng/ml), delayed T(max) (3.17 h) and higher MRT value (147.82 h) (p < 0.05).

CONCLUSION

This sustained activity was due to the controlled release of drug into the systemic circulation with expected increase in the patient compliance and prevention of nocturnal enuresis.