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After oral administration, poor permeability often limits the rate at which drugs are absorbed through the intestinal epithelium. Enhancing drug permeability is crucial for effective therapy, and several strategies have been developed to overcome this challenge.One effective strategy involves the use of lipid-based formulations. These formulations enhance dissolution and solubility, targeting physiological mechanisms to increase drug absorption. This includes stimulating bile salt secretion,...
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Updated: Mar 8, 2026

A Method for Determination and Simulation of Permeability and Diffusion in a 3D Tissue Model in a Membrane Insert System for Multi-well Plates
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Solubility-Permeability-Matrix Interplay in Percutaneous Absorption Exemplified by Theophylline.

Sophia Engel1, Jozef Al-Gousous1, Christiane Grünewald2

  • 1Department of Biopharmaceutics and Pharmaceutical Technology, Johannes Gutenberg University Mainz, 55128, Mainz, Germany.

AAPS Pharmscitech
|March 6, 2026
PubMed
Summary
This summary is machine-generated.

Aminophylline shows higher skin penetration than theophylline in transdermal patches. This is due to its formulation as a suspension, enhancing its chemical potential for better drug delivery via aqueous pathways.

Keywords:
AminophyllinePermeabilityStratum corneumTheophyllineTransdermal patch

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Area of Science:

  • Pharmaceutical Sciences
  • Biomaterials Science
  • Drug Delivery

Background:

  • The stratum corneum is a major obstacle for transdermal delivery of hydrophilic and ionized drugs like aminophylline.
  • Understanding the interplay between drug solubility, skin permeability, and patch matrix is crucial for effective transdermal formulations.

Purpose of the Study:

  • To investigate the solubility-permeability-matrix interplay for aminophylline and theophylline in hydroxypropyl methylcellulose (HPMC) and silicone-based Bio-PSA transdermal patches.
  • To evaluate the impact of different penetration enhancers on the transdermal delivery of these model drugs.

Main Methods:

  • Utilized Franz diffusion cells with porcine ear skin for in vitro skin permeation studies.
  • Conducted complementary release studies using dialysis membranes.
  • Assessed the effects of penetration enhancers geraniol and Transcutol P on drug permeation.

Main Results:

  • Aminophylline demonstrated significantly higher transdermal flux compared to theophylline in both HPMC and Bio-PSA matrices.
  • High thermodynamic activity of suspended aminophylline enhanced chemical potential gradients, facilitating permeation through aqueous pathways.
  • Geraniol effectively increased skin permeation by disrupting stratum corneum lipids, while Transcutol P showed a modest effect due to limited matrix interaction and release.

Conclusions:

  • Drug solubility and enhancer properties are critical for the transdermal delivery of hydrophilic drugs.
  • Optimizing matrix parameters such as thickness, hydration, and release characteristics is essential for maximizing the solubility-permeability interplay in transdermal patches.