Category: Formulation and Quality
Purpose: TAC is the most commonly used immunosuppressant in post transplantation maintenance therapy. Being a highly potent drug, it requires a strict control of trough concentration in whole blood to avoid side effects. Developing a transdermal drug delivery system for TAC can help improve its PK profile by bypassing the GI absorption and first pass effect.
Methods: To deliver a large molecule such as TAC, we identify penetration enhancers that are capable of enhancing TAC’s permeation across porcine ear skin using Franz diffusion cells. Two penetration enhancers, phenylpiperazine and TPGS, are commonly used in transdermal formulations and FDA approved are incorporated into our matrix patch. The matrix type transdermal patch using a Eudragit RL100 and PVP K30 at 2:8 ratio as matrix formers is developed to deliver TAC.
Results: Here we have demonstrated the feasibility of delivering such molecule across the skin barrier using a pair of synergistic enhancers, phenylpiperazine and TPGS. By incorporating the drug and penetration enhancers into a matrix type transdermal patch using Eudragit RL100 and PVP K30 at 2:8 ratio as matrix formers, the patch is found to deliver TAC across pig ear skin in Franz diffusion experiment at a rate of 5.11±0.71 g/cm 2 /hr. The release rate is confirmed in rat PK studies.
Conclusion: The patch size of 2.5 cm 2 is shown to be able to maintain TAC concentration within the therapeutic range for up to 7 days. The patch size can be cut to accommodate different release rates, allowing for customized dosing based on weight and scaling to other animal models.