Development and Evaluation of a Novel Drug in Adhesive Transdermal System of Levodopa and Carbidopa

Purpose

Administration of levodopa along with carbidopa increases the availability of dopamine in the mid-brain, and this combination thereby is used in the treatment of parkinsonism. However, concomitant delivery of levodopa with carbidopa in oral therapy is limited by several issues and an alternative route would be advantageous. The current study assesses the feasibility of co-administration of levodopa and carbidopa through skin using a drug in adhesive transdermal system.

Methods

Drug in adhesive transdermal system containing levodopa (5 % w/w) and carbidopa (2.5 % w/w) (1 cm² area) was fabricated and assessed for in vitro drug release, ex vivo permeation, and in vivo pharmacokinetics in rat model.

Results

In vitro dissolution profiles indicated a biphasic pattern with an initial burst effect for both levodopa and carbidopa, although the drug release rate was relatively higher for carbidopa. Ex vivo permeation studies showed higher steady-state flux for levodopa (53.77?±?6.94 μg/cm²/h) and carbidopa (23.81?±?4.06 μg/cm²/h). In vivo studies revealed that the concomitant transdermal delivery of levodopa with carbidopa significantly changed the pharmacokinetic parameters of levodopa.

Conclusions

Given the promising results, this study concludes that the transdermal delivery route could be a feasible alternative to oral therapy for the successful delivery of levodopa in Parkinson’s disorder.