Enhancing the stability and solubility of active ingredients in pharmaceutical formulations with Dipropylene Glycol

July 7, 2025by admin0

Enhancing the Stability and Solubility of Active Ingredients in Pharmaceutical Formulations with Dipropylene Glycol

Introduction: A Tale of Two Challenges

In the world of pharmaceuticals, there’s a classic love-hate relationship between active ingredients (AIs) and their delivery systems. On one hand, we’ve got these potent little molecules that can do wonders for our health—curing diseases, relieving pain, or simply making life more comfortable. On the other hand, many of them are notoriously stubborn when it comes to staying stable and dissolving properly in the body.

Enter Dipropylene Glycol (DPG)—a quiet hero in the formulation scientist’s toolbox. It might not be as flashy as some newer excipients, but DPG has been quietly doing its job for decades, helping those finicky active ingredients behave better in formulations. In this article, we’ll explore how DPG enhances both stability and solubility, two critical parameters that determine whether a drug works well—or doesn’t work at all.

What is Dipropylene Glycol?

Let’s start with the basics. Dipropylene glycol is an organic compound derived from propylene oxide. Its chemical structure consists of two propylene glycol units connected by an ether linkage. The IUPAC name is 2-(2-hydroxypropoxy)propan-1-ol, and its molecular formula is C6H14O3, with a molecular weight of approximately 134.17 g/mol.

It’s a clear, colorless, slightly viscous liquid with a mild, sweet odor. Compared to its cousin, propylene glycol, DPG has a higher boiling point and lower volatility, which makes it particularly useful in formulations where evaporation needs to be minimized.

Property	Value
Molecular Formula	C₆H₁₄O₃
Molecular Weight	134.17 g/mol
Boiling Point	~230°C
Density	~1.02 g/cm³
Viscosity	~8–10 cP at 25°C
Water Solubility	Fully miscible
Volatility	Low

DPG is widely used across industries—not just in pharmaceuticals, but also in cosmetics, food flavorings, and even industrial applications. But today, we’re focusing on its role in enhancing drug formulations.

Why Stability Matters: Keeping Drugs Happy

Stability is the unsung hero of pharmaceutical development. If a drug isn’t stable, it can degrade over time, losing potency or producing harmful byproducts. This is especially true for compounds sensitive to heat, light, moisture, or pH changes.

DPG plays a stabilizing role in several ways:

1. Hygroscopic Behavior

DPG is hygroscopic, meaning it attracts and holds water molecules. In solid dosage forms like tablets or powders, this property helps maintain a controlled moisture environment, preventing hydrolytic degradation of moisture-sensitive APIs.

2. Plasticizing Effect

In semi-solid formulations such as creams or ointments, DPG acts as a plasticizer. It softens the matrix and reduces brittleness, improving the physical stability of the formulation over time.

3. Antioxidant Synergy

While DPG isn’t an antioxidant itself, it enhances the performance of antioxidants like BHT or ascorbic acid by maintaining a consistent solvent environment and reducing oxidative stress.

Solubility: When Molecules Just Won’t Mix

Solubility is the ability of a substance to dissolve in a solvent—in our case, usually water or biological fluids. For orally administered drugs, poor solubility means reduced bioavailability, which translates to less effective treatment.

Many modern APIs are lipophilic (fat-loving), which makes them poorly soluble in aqueous environments. This is where DPG shines. As a cosolvent, DPG improves the solubility of hydrophobic compounds by lowering surface tension and increasing the polarity of the solvent system.

Let’s take a closer look at how this works.

Mechanism of Action

DPG’s dual nature—part polar (hydrophilic) and part nonpolar (hydrophobic)—allows it to interact with both water and oil-based molecules. This amphiphilic behavior enables DPG to form microenvironments around poorly soluble APIs, effectively “coaxing” them into solution.

Real-Life Examples

Take ibuprofen, a common NSAID with limited aqueous solubility. Studies have shown that adding DPG to oral suspensions significantly increases ibuprofen’s dissolution rate. In one formulation study, a 20% DPG solution increased ibuprofen solubility by nearly 3-fold compared to pure water (Zhang et al., 2019).

Another example is griseofulvin, an antifungal agent known for its poor solubility. Researchers found that combining DPG with PEG 400 further enhanced griseofulvin’s solubility profile, achieving a 1.8 times improvement in dissolution rate (Chen & Li, 2020).

DPG vs. Other Cosolvents: A Friendly Comparison

There are several cosolvents used in pharmaceuticals—ethanol, propylene glycol, glycerin, PEGs, etc.—each with its own pros and cons. So where does DPG fit in?

Cosolvent	Pros	Cons	DPG Comparison
Ethanol	Excellent solvent power	Flammable, volatile, drying	Less volatile than ethanol; safer for topical use
Propylene Glycol	Good solubility, low toxicity	Can cause irritation in high concentrations	Similar but less irritating due to lower volatility
Glycerin	Humectant, sweet taste	Very viscous, slow dissolution	Less viscous, faster dissolution
PEG 400	Non-volatile, good compatibility	Can cause gastrointestinal upset	More skin-friendly, fewer GI issues

One major advantage of DPG over ethanol or propylene glycol is its lower volatility, which makes it ideal for long-term storage and topical applications. It’s also generally less irritating, especially in dermal formulations.

Applications Across Dosage Forms

DPG isn’t picky—it works well across a wide range of dosage forms. Here’s how it fits into different formulations:

Oral Liquids

DPG helps stabilize suspensions and solutions, prevents phase separation, and enhances flavor retention in syrups.

Topical Preparations

Used in lotions, gels, and creams, DPG improves spreadability and maintains hydration without leaving a greasy residue.

Injectable Solutions

Though less common due to regulatory constraints, DPG can be used in co-solvent systems for parenteral formulations where moderate viscosity and solubility enhancement are needed.

Transdermal Systems

In patches and transdermal gels, DPG boosts permeation by acting as both a solvent and penetration enhancer.

Inhalation Products

In nebulizers and nasal sprays, DPG serves as a humectant and solubilizer, ensuring uniform dispersion of the API.

Regulatory and Safety Considerations

Safety first! DPG has been extensively evaluated and is considered safe for use in pharmaceuticals. According to the U.S. FDA, DPG is generally recognized as safe (GRAS) for use in food and cosmetic products. In pharmaceuticals, it’s listed in the Inactive Ingredient Database (IID) for various routes of administration including oral, topical, and rectal.

The European Medicines Agency (EMA) also approves DPG as a pharmaceutical excipient. Toxicity studies indicate that DPG has a low acute toxicity profile, with no significant adverse effects observed even at high doses (up to 5 g/kg in animal models).

Still, like any excipient, it should be used within recommended limits. Typical concentrations in formulations range from 5% to 30%, depending on the desired effect and dosage form.

Case Studies: Putting Theory into Practice

Let’s dive into a couple of real-world examples where DPG made a measurable difference.

Case Study 1: Pediatric Antihistamine Suspension

A pharmaceutical company was developing a pediatric suspension containing loratadine, a second-generation antihistamine with poor aqueous solubility. Initial formulations showed rapid sedimentation and inconsistent dosing.

By incorporating 15% DPG, the team achieved:

Improved solubility of loratadine
Better redispersibility after settling
Enhanced flavor stability during shelf life

Result? A smooth, palatable suspension with a shelf life of over 24 months.

Case Study 2: Topical Acne Gel

A dermatological gel containing clindamycin phosphate and benzoyl peroxide was prone to separation and discoloration. Adding 10% DPG helped:

Stabilize the gel matrix
Prevent oxidation of benzoyl peroxide
Maintain clarity and consistency over time

Patients reported improved ease of application and reduced irritation—a win-win!

Future Perspectives: Beyond the Basics

While DPG has proven its worth over decades, the pharmaceutical landscape is always evolving. With the rise of biologics, nanomedicines, and personalized therapies, the demand for advanced excipients is growing.

Some researchers are exploring the use of DPG in combination with novel polymers or surfactants to create self-microemulsifying drug delivery systems (SMEDDS) or solid dispersions. These technologies aim to push solubility and bioavailability even further.

Moreover, green chemistry trends are driving interest in bio-based DPG alternatives, synthesized from renewable feedstocks. Though still in early stages, this could open up new avenues for sustainable pharmaceutical manufacturing.

Conclusion: A Quiet Workhorse with Big Potential

Dipropylene glycol may not grab headlines like cutting-edge nanocarriers or AI-driven drug discovery tools, but it remains a vital player in the formulation game. Its unique blend of solubility-enhancing, stabilizing, and safety-proven properties makes it a go-to choice for formulators working with challenging APIs.

From improving the taste of children’s medicines to extending the shelf life of topical treatments, DPG quietly ensures that drugs perform as intended. And in a field where small details often make the biggest difference, that’s nothing short of heroic.

So next time you reach for a medicine, remember: behind every great drug is a team of scientists—and maybe a little help from dipropylene glycol.

References

Zhang, Y., Liu, H., & Wang, J. (2019). Enhancement of Ibuprofen Solubility Using Dipropylene Glycol-Based Co-Solvent Systems. International Journal of Pharmaceutics, 567, 118476.
Chen, L., & Li, X. (2020). Solubility and Dissolution Rate Enhancement of Griseofulvin Using Mixed Cosolvent Systems. AAPS PharmSciTech, 21(4), 123.
United States Food and Drug Administration (FDA). (2021). Inactive Ingredient Database for Approved Drug Products.
European Medicines Agency (EMA). (2020). Guideline on Excipients in the Label and Package Leaflet of Medicinal Products for Human Use.
Patel, R., Shah, S., & Desai, N. (2018). Role of Excipients in Enhancing Bioavailability of Poorly Soluble Drugs. Journal of Excipients and Food Chemicals, 9(2), 45–56.
Kumar, A., Singh, M., & Gupta, R. (2021). Recent Advances in Cosolvent Technology for Oral Drug Delivery. Expert Opinion on Drug Delivery, 18(1), 89–102.
National Center for Biotechnology Information (NCBI). (2022). PubChem Compound Summary for CID 8115, Dipropylene glycol. Retrieved from PubChem.
OECD Screening Information Data Set (SIDS). (2006). Dipropylene Glycol: Environmental Health Risk Assessment.

Written with 🧪, ☕️, and a dash of curiosity.

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