Alternative Delivery Approaches for Levothyroxine
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Hypothyroidism affects almost 2-5% of the world population and requires lifelong thyroxine replacement therapy. Oral Administration of levothyroxine (T4) encounters enormous pathophysiological and pharmacological challenges that sometimes lead to therapeutic failure. The aim of this study was to conduct proof-of-principle studies which enables possible development of non-invasive (respiratory, transdermal) T4 delivery systems. Preformulation (solubility, stability) and biopharmaceutical (in-vitro absorption, gene expression) studies were conducted using Calu-3 (respiratory cell line) and Strat-M® (artificial skin membrane). Transport of T4 across Calu-3 cells suggested involvement of active transport systems which correlated with expression of thyroxine transporters (MCT8, MCT10, OATP1A2, OATP4A). However, T4 permeation across Strat-M® was non-existent even after using chemical absorption enhancers. In conclusion, data from these studies indicated that T4 may be successfully delivered via the respiratory route. However, successful transdermal delivery may require a reversible, but mildly invasive approach.