Why Is Propylene Glycol (Pg) Selected For Transdermal Drug Delivery? Optimize Solubility & Research Precision

Propylene Glycol (PG) is primarily selected as a solvent in donor solutions because it effectively solubilizes poorly soluble pharmaceutical compounds while providing a stable, predictable baseline for permeation studies. Beyond simply dissolving drugs like berberine or baicalin, PG acts as a co-enhancer that ensures the drug reaches a saturated state at the administration site, which is critical for driving transdermal delivery.

Core Insight: While Propylene Glycol is a powerful solvent, its greatest value in research lies in its predictability. Because its impact on the skin barrier is constant and well-documented, it allows scientists to accurately isolate and measure the specific effects of other added penetration enhancers without experimental noise.

The Mechanics of Solubility and Saturation

Tackling Poorly Soluble Drugs

Many potent pharmaceutical agents, such as berberine or baicalin, suffer from poor solubility in water.

Propylene Glycol acts as an excellent solvent to overcome this hurdle. By dissolving these difficult compounds, PG brings them into a liquid phase, which is the first prerequisite for any transdermal absorption.

Driving Delivery Through Saturation

Successful transdermal delivery often relies on the thermodynamic activity of the drug.

Mechanistic studies utilize high concentrations of PG (e.g., 80% solutions) to ensure the drug reaches a saturated state or a specific mass concentration. This saturation maximizes the driving force required to push the drug across the skin barrier.

##Ideally Suited for Mechanistic Studies

A Stable Baseline for Comparison

When formulating transdermal systems, researchers often add potent enhancers, such as Borneol, to further boost absorption.

To determine if these added enhancers are effective, the background solvent must behave predictably. If the solvent's interaction with the skin is erratic, it becomes impossible to tell if increased absorption is due to the Borneol or the solvent itself.

Documented Interaction with Stratum Corneum

Propylene Glycol is favored because its impact on the stratum corneum (the skin's outer layer) is well-documented and constant.

This stability allows for the accurate isolation of variables. Researchers can confidently attribute any additional penetration enhancement to the specific additives being tested, rather than fluctuations in the solvent's behavior.

Broader Formulation Utility

Improving Patch Flexibility

While its primary role in donor solutions is chemical, PG serves a structural role in polymer-based patches.

It acts as a plasticizer by inserting itself between polymer chains, such as Hydroxypropyl Methylcellulose (HPMC).

Preventing Structural Failure

This "molecular cushioning" increases the folding endurance of the patch.

It ensures the patch possesses sufficient elasticity to follow body contours without cracking or breaking, maintaining integrity even on moving skin surfaces.

Understanding the Methodological Context

The Distinction Between "Constant" and "Inert"

It is critical to understand that PG is not pharmacologically inert regarding the skin barrier.

It does impact the structure of the stratum corneum. However, the advantage is that this impact is known and consistent.

Avoiding False Negatives in Research

A common pitfall in formulation science is using a solvent with variable skin interaction.

By using PG, you avoid the risk of experimental noise obscuring the true efficacy of your active ingredients or novel enhancers.

Making the Right Choice for Your Goal

When selecting Propylene Glycol for your preparation, clarify whether your need is chemical or mechanical.

If your primary focus is optimizing drug availability: Leverage PG’s ability to reach saturation concentrations (e.g., 80%) to maximize the thermodynamic drive of poorly soluble drugs.
If your primary focus is comparative research: Rely on PG as a background solvent to create a stable control environment for testing the efficacy of novel penetration enhancers like Borneol.
If your primary focus is patch integrity: Utilize PG as a plasticizer to ensure polymer matrices remain flexible and conformable to the patient's skin.

Propylene Glycol offers the dual advantage of chemical power for dissolution and the scientific reliability required for rigorous mechanistic study.

Summary Table:

Function	Mechanism	Key Advantage for Formulators
Solubility	Dissolves poorly soluble agents (e.g., Berberine)	Brings pharmaceutical agents into liquid phase
Saturation	High concentration (80%) driving force	Maximizes thermodynamic drug delivery rate
Research Baseline	Documented, constant skin interaction	Isolates effects of added enhancers like Borneol
Plasticizer	Inserts between polymer chains (HPMC)	Increases folding endurance and patch elasticity

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References

Chang Yang, Xinyuan Shi. Multiscale study on the enhancing effect and mechanism of borneolum on transdermal permeation of drugs with different log P values and molecular sizes. DOI: 10.1016/j.ijpharm.2020.119225

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