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Complex Drug Delivery Systems: Controlling Transdermal Permeation Rates with Multiple Active Pharmaceutical Ingredients

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Abstract

A transdermal drug delivery system (TDDS) is generally designed to deliver an active pharmaceutical ingredient (API) through the skin for systemic action. Permeation of an API through the skin is controlled by adjusting drug concentration, formulation composition, and patch design. A bilayer, drug-in-adhesive TDDS design may allow improved modulation of the drug release profile by facilitating varying layer thicknesses and drug spatial distribution across each layer. We hypothesized that the co-release of two fixed-dose APIs from a bilayer TDDS could be controlled by modifying spatial distribution and layer thickness while maintaining the same overall formulation composition. Franz cell diffusion studies demonstrated that three different bilayer patch designs, with different spatial distribution of drug and layer thicknesses, could modulate drug permeation and be compared with a reference single-layer monolith patch design. Compared with the monolith, decreased opioid antagonist permeation while maintaining fentanyl permeation could be achieved using a bilayer design. In addition, modulation of the drug spatial distribution and individual layer thicknesses, control of each drug’s permeation could be independently achieved. Bilayer patch performance did not change over an 8-week period in accelerated stability storage conditions. In conclusion, modifying the patch design of a bilayer TDDS achieves an individualized permeation of each API while maintaining constant patch composition.

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Acknowledgments

Research reported in this paper was supported by the National Institute on Drug Abuse (NIDA) of the NIH under project grant R44DA042639 awarded to Cassava Sciences, Inc. We also acknowledge the use of tissues procured through the National Disease Research Interchange (NDRI) with support from NIH grant U42OD11158.

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Authors and Affiliations

  1. Molecular Pharmaceutics and Drug Delivery, College of Pharmacy, The University of Texas at Austin, 2409 West University Ave A1920 PHR 1.116, Austin, Texas, 78712, USA

    Daniel A. Davis, Patricia P. Martins, Robert O. Williams III, Hugh D. C. Smyth & Zachary N. Warnken

  2. Cassava Sciences Inc., 7801 North Capital of Texas Highway, Suite 260, Austin, Texas, 78731, USA

    Michael S. Zamloot & Shawn A. Kucera

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  1. Daniel A. Davis
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  2. Patricia P. Martins
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Correspondence to Zachary N. Warnken.

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Davis, D.A., Martins, P.P., Zamloot, M.S. et al. Complex Drug Delivery Systems: Controlling Transdermal Permeation Rates with Multiple Active Pharmaceutical Ingredients. AAPS PharmSciTech 21, 165 (2020). https://doi.org/10.1208/s12249-020-01682-4

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