Design of a tulobuterol patch with improved mechanical properties: effect of transdermal permeation enhancers on the release process of metal ligand-based acrylic pressure-sensitive adhesives

The aim of this study was to design a tulobuterol (TUL) patch with good penetration behavior and mechanical properties. Particular attention was paid to the effect of transdermal permeation enhancers on the release process of metal ligand-based acrylic pressure-sensitive adhesive (AA-NAT/Fe 3+ ). The type and dosage of the enhancers were screened by in vitro transdermal penetration in rat skin. The optimized formulation was evaluated in a pharmacokinetic study in rats. Furthermore, the molecular mechanism by which Azone (AZ) improves the release rate of TUL from AA-NAT/Fe 3+ was investigated by FT-IR, shear strength test, rheological study, and molecular simulation. As a result, the optimized formula using AA-NAT/Fe 3+ showed better mechanical properties compared to commercial products. Meanwhile, the AUC 0-t and C max of the optimized patch were 1045 ± 89 ng/mL·h and 106.8 ± 28.5 ng/mL, respectively, which were not significantly different from those of the commercial product. In addition, AZ increased the mobility of the pressure-sensitive adhesive (PSA) rather than decreasing the drug-PSA interaction, which was the main factor in enhancing TUL release from the patch. In conclusion, a TUL transdermal drug delivery patch was successfully developed using metal-coordinated PSA, and a reference was provided for the design of metal-coordinated acrylic PSA for transdermal patch delivery applications. Graphical Abstract