Realizing zero-order controlled transdermal drug permeation through competing doubly ionic H-bond in patch.

Area of Science:

• Pharmaceutical Sciences
• Materials Science
• Drug Delivery

Background:

• Transdermal drug delivery systems (TDDS) offer controlled drug administration, but achieving zero-order release from drug-in-adhesive patches remains a significant challenge.
• Existing TDDS often struggle with consistent drug release kinetics, impacting therapeutic efficacy and patient compliance.

Purpose of the Study:

• To develop a novel strategy for achieving zero-order controlled drug skin delivery from transdermal patches.
• To stabilize drug concentration within the adhesive matrix using concentration-dependent competitive interactions.
• To evaluate the efficacy of a hydroxyphenyl (HP) and polydimethylaminoethyl acrylate (EA) adhesive system for controlled release of model drugs.

Main Methods:

• Utilized Clonidine (CLO) and Granisetron (GRA) as model drugs with high skin permeability.
• Incorporated polydimethylaminoethyl acrylate (EA) as an excipient to interact with hydroxyphenyl (HP) adhesive.
• Conducted drug release, skin permeation, and pharmacokinetic studies.
• Characterized molecular interactions using FT-IR, 1H NMR, and XPS.
• Employed dynamic simulation and molecular docking to elucidate the competitive interaction mechanism.

Main Results:

• The HP-EA adhesive system demonstrated good zero-order fitting for both CLO and GRA skin permeation (r values of 0.994 and 0.998).
• Pharmacokinetic studies of the CLO patch showed a sustained plateau phase for approximately 52 hours without altering the area under the concentration-time curve (AUC).
• Mechanism studies revealed EA acts as a buffer, stabilizing the concentration of neutral drug species released.

Conclusions:

• The developed transdermal drug delivery system effectively achieves zero-order controlled drug skin delivery.
• The concentration-dependent competitive interaction strategy broadens the understanding of molecular mechanisms in TDDS.
• This approach holds promise for advancing the development of zero-order drug delivery in transdermal patches.