Why Is A Mixture Of Ethanol And Propylene Glycol Used As A Solvent System In Reservoir-Type Transdermal Patches?

The combination of ethanol and propylene glycol is utilized in reservoir-type transdermal patches to solve the dual challenge of dissolving poorly soluble drugs and effectively driving them through the skin barrier. By working synergistically, this solvent system maximizes the drug's saturation within the patch while simultaneously altering the skin's properties to allow for permeation.

Core Takeaway This solvent mixture functions as a powerful permeation enhancement system. Ethanol increases the fluidity of skin lipids, while propylene glycol improves the drug's ability to partition into the tissue, creating an optimized concentration gradient that significantly increases transdermal flux.

The Mechanics of Solubility and Flux

Overcoming Solubility Limits

Many potent drugs are poorly soluble, making them difficult to load into a patch in sufficient quantities.

The primary function of the ethanol and propylene glycol mixture is to significantly enhance the solubility of these drugs within the patch reservoir.

Creating a Concentration Gradient

Effective transdermal delivery relies on a strong driving force, known as the concentration gradient.

By maximizing the amount of dissolved drug in the reservoir, this solvent system creates a high concentration pressure that pushes the active ingredients out of the patch and toward the skin.

Mechanisms of Skin Penetration

Ethanol: Increasing Lipid Fluidity

Ethanol acts as more than just a solvent; it actively modifies the skin environment.

It promotes penetration by interacting with the lipids in the skin, increasing their fluidity. This "loosening" effect reduces the barrier resistance of the stratum corneum.

Propylene Glycol: Improving Partitioning

Propylene glycol penetrates the stratum corneum and modifies the solubility properties of the skin tissue itself.

This improves the drug's partition coefficient, meaning the drug becomes more chemically inclined to leave the patch and enter the skin layers.

Optimizing Transdermal Flux

The combined use of these two solvents results in a higher transdermal flux than either could achieve alone.

While ethanol disrupts the barrier, propylene glycol ensures the drug moves efficiently across that barrier, optimizing the delivery rate of hydrophobic drugs.

Physical Formulation Benefits

Plasticization and Flexibility

Beyond chemical delivery, propylene glycol serves a mechanical role as a plasticizer.

It improves the flexibility of the polymer film, ensuring the patch remains comfortable and maintains proper adhesion to the skin during movement.

Understanding the Trade-offs

Balancing Potency with Stability

While high solvent concentrations increase delivery rates, the formulation must remain stable.

Using propylene glycol as a regulated pharmaceutical excipient is critical because it enhances bioavailability while ensuring the safety and stability of the final product.

Barrier Resistance Reduction

The mechanism of action relies on reducing the skin's natural barrier resistance.

Formulators must carefully balance this reduction to achieve therapeutic levels of drug delivery without compromising the skin's integrity or causing excessive irritation.

Making the Right Choice for Your Goal

To apply this to your specific formulation strategy, consider your primary objective:

If your primary focus is maximizing drug delivery rates: Prioritize the synergistic ratio of ethanol to propylene glycol to maximize the concentration gradient and lipid fluidity.
If your primary focus is patch wearability and adhesion: Ensure the concentration of propylene glycol is sufficient to act as a plasticizer, improving the flexibility of the polymer film.

Ultimately, the ethanol-propylene glycol system is the industry standard for reservoir patches because it simultaneously solves the chemical problem of solubility and the biological problem of skin barrier resistance.

Summary Table:

Function	Mechanism of Action	Benefit to Patch Performance
Ethanol	Increases skin lipid fluidity	Reduces barrier resistance for faster absorption
Propylene Glycol	Improves partitioning & acts as a plasticizer	Enhances drug entry into tissue and patch flexibility
Synergistic Blend	Creates high concentration gradient	Maximizes transdermal flux for poorly soluble drugs
Polymer Support	Stabilizes the solvent system	Ensures consistent drug release and skin adhesion

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References

Zhen Yang, Huimin Hou. Enhancement of skin permeation of bufalin by limonene via reservoir type transdermal patch: Formulation design and biopharmaceutical evaluation. DOI: 10.1016/j.ijpharm.2013.02.048

This article is also based on technical information from Enokon Knowledge Base .