Transdermal Delivery of Lamivudine: Effect of Vehicles on Permeation through Rat Skin

C J Mbah, P F Uzor, A A Attama

Abstract
Objective: The purpose of the present study was to investigate the effect of vehicles, namely: water, ethanol, propylene glycol, their binary combinations and microemulsion formulation on the permeation of lamivudine across excised rat epidermis in order to select a suitable vehicle for use in the development of a transdermal therapeutic system.
Methods: The investigation was done using the modified Franz’s diffusion cell. The skin permeation mechanism of lamivudine from 1% polysorbate-80 and optimized microemulsion formulation was evaluated by fourier transform infrared (FTIR) spectral analysis and differential scanning calorimetry (DSC) thermogram respectively.
Results: Besides propylene glycol, all the vehicles investigated showed a significant (p<0.05) increase in the permeation flux of lamivudine compared to the control flux (3.23 ± 0.62 μg/cm2/h). Of the vehicles investigated also, only 1% polysorbate-80 and optimized microemulsion showed a 7-fold increase in transdermal flux (21.9 ± 0.55 and 22.1 ± 0.62 μg/cm2/h respectively) of lamivudine across the rat skin compared to lamivudine aqueous solution (control). The results of the biophysical studies suggest disruption of lipid bilayers and/or denaturation of the intracellular keratin of the stratum corneum to be the main contributions for improved skin permeation.
Conclusion: It was concluded that microemulsion and polysorbate -80 were good vehicles for the transdermal delivery of lamivudine.

Key words: KEYWORDS: Antiretroviral, lamivudine, in vitro permeability across rat skin, UV spectrophotometry.