Transdermal Permeation Enhancement of Lamotrigine Using Terpenes

Abstract

The objective of this research was to study the permeation of lipophilic drug lamotrigine (LTG) using terpenes as permeation enhancers. Transdermal patches were formulated using one of the permeation enhancers namely Nerolidol, Limonene, Linalool, Carvone, Fenchone, Menthol, Geraniol, Farnesol. LTG patches were prepared by solvent casting method. The prepared patches were evaluated for drug content, thickness, and weight variation, folding endurance, moisture uptake, water vapour transmission, in-vitro diffusion study, ex-vivo permeation study and skin irritation study. Fourier Transform Infrared study revealed no interaction among the drug, polymers and terpenes used in the present study. The in vitro drug release studies were performed in 7.4 pH phosphate buffer using a Franz diffusion cell. Different formulations were prepared and variations in drug release profiles were observed. The cumulative percentage drug release of different terpenes was found to be in the order - limonene > fenchone > linalool > menthol > geraniol > carvone > nerolidol> farnesol. From the “n” values of optimized formulations which ranged from 0.6 to 0.7, it is evident that the release mechanism follows non-fickian type of diffusion which might be due to a combination of lipophilic and hydrophilic polymers used. Enhancement in drug release and ex-vivo skin penetration of LTG was found to depend on nature and concentration of terpenes and polymers. The skin irritation test was performed in rabbits and these results suggested that both placebo and drug-loaded films produced negligible erythema and edema compared to 1% sodium lauryl sulfate solution as the standard irritant. Formulations LLH3Lm (2.5%), LLH3Lm (5%) with Eudragit RL100, HPMC E15LV at 2.5% and 5% limonene concentration were found to show optimum drug release, improved permeability, steady state transdermal flux and reduced lag time (P<0.001) when compared to control formulation.