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Models and Methods to Evaluate Transport of Drug Delivery Systems Across Cellular Barriers
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Realizing zero-order controlled transdermal drug permeation through competing doubly ionic H-bond in patch.

Shuai Zhang1, Quanzhi Zhang1, Runmei Xu1

  • 1Department of Pharmaceutical Sciences, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang, Liaoning 110016, China.

International Journal of Pharmaceutics
|September 13, 2023
PubMed
Summary
This summary is machine-generated.

This study introduces a novel strategy for transdermal drug delivery systems (TDDS) by stabilizing drug concentration in adhesives. This approach enables zero-order controlled drug release from patches, overcoming previous challenges in drug delivery.

Keywords:
Hydroxyphenyl-polyacrylate adhesivePolydimethylaminoethyl acrylateTransdermal drug delivery systemZero-order

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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.