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
Summary
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.
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.
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