Micellar Solubilization and its Importance in Pharmacy

By Fatma Sobih

Contact the author: fatmasobih18@gmail.com

Fatima is a pharmacist. She is interested in searching for and writing about chemicals and their importance in pharmaceutical sciences.

Through this article, you will learn about
1. Role of micellar solubilization in pharmacy.
2. The use of polymeric micelles in anti-cancer drug delivery.
3. Physical and Chemical Modifications of Micelles.
4. Notable drugs that involve the use of micelles.

What are Micelles?

Surfactants, also referred to as surface active agents, are known to play an essential role in many processes of importance in both primary and applied sciences, like a detergent, which, when added to a liquid, lowers its surface tension, thereby increasing its diffusion and moisturizing properties. In textile dyeing, surfactants help the dye penetrate the fabric evenly. It is used to distribute hydrous suspensions of insoluble pigments and perfumes. An essential feature of surfactants is the formation of colloid-sized groups in mixtures called micelles.

Detergent monomers in aqueous solutions participate in two forms of primary phase transitions. First, the crystallization of monomers in a hydrous solution occurs, while almost all detergents used in membrane biochemistry do not crystallize. Second, the detergent’s monomers self-link to form structures called micelles.

Figure 1. The thermodynamic equilibrium represents the reversible monomer-micelle. The red circles represent the hydrophilic heads, and the blue curved lines represent the hydrophobic surfactant tails.

Micelles are a standard phenomenon with many surfactants, and their size is determined by their aggregation number. The distribution of water within its structure is anisotropic. When the water concentration decreases from the surface towards the core of the micelle, with a completely lipophilic core. Thus, the location of the drug dissolved in a micelle will depend upon its polarity: non-polar molecules are dissolved within the core of the micelle, and at the intermediate position, the substance with intermediate polarity is distributed in it with the surfactant molecules.

Role of Micellar Solubilization in Pharmacy

This figure shows how drugs can be absorbed into micelles.

1. One of the significant properties of micelles in pharmacy is their ability to solubilize molecules of poorly soluble nonpolar pharmaceutical drugs within the core of the micelle and the polar molecule is absorbed on the shell of the micelle. Thus, micelles are used to solubilize drugs, forming amphiphiles, resulting in increased water solubility of sparingly soluble drugs and improving drug bioavailability.

How drugs can be absorbed on micelles:

Hydrophilic drugs can be adsorbed on the surface of the micelle (1).
Intermediate-solubilizing drugs are located in intermediate positions within the micelle between the hydrophilic head groups of PEO micelles (2).
In the barrier layer between the hydrophilic groups and the first few carbon atoms of the hydrophobic group, which is the outer core (3).
Completely insoluble hydrophobic drugs are located in the inner core of the micelle (4).

2. Thus, micelles have important advantages as drug carriers, such as:

The ability to solubilize drugs leads to an increase in the solubility of poorly soluble drugs.
Reduce toxicity.
Improve the permeability of the drug so that it can cross physiological barriers more easily and, therefore, improve bioavailability.
Protect the drug from any biological inactivation.

The Usage of Polymeric Micelles in Anti-Cancer Drug Delivery

Polymeric micelles have gained popularity for their many advantages in drug delivery over traditional drug therapy methods. Polymeric micelles are nanoconstructs of amphiphilic copolymers that are self-assembling and have a core-shell structure. Among their many advantages are their ability to solubilize many poorly soluble pharmaceutical agents, their longevity, biocompatibility, and high stability in vivo and in vitro.

The use of polymeric micelles in drug delivery has been studied extensively over the years, and one of the most prominent areas of study is their use in anticancer drug delivery. Anti-cancer drugs are typically hydrophobic, and this becomes a problem in parenteral administration when undissolved drugs can lead to the blood vessels becoming embolized before the drug can reach the tumor. Polymeric micelles are used to solve this problem, as they can solubilize the drug and increase its bioavailability by protecting it from inactivation.

Furthermore, micelles circulate longer in the blood due to their small size. This longer circulation time allows micelles to accumulate more in areas of leaky or defective vasculature, like tumors.

Other Applications

It is widely used in electrophoresis and chromatography as a separation method.
They are called enabling nanoparticles to be effective in various applications, such as gene delivery, diagnostic imaging, and medicine.
The micelles act as emulsifiers when the surfactants are above the critical micelle concentration, allowing the compound to dissolve, which would normally be insoluble. For example, detergents remove lipophilic substances that are less soluble and cannot be removed with the help of water alone.
It is required in the human body and plays a vital role in removing complex fats and fat-soluble vitamins.
Micellar cleansers can be used for all skin types.
Improving the aqueous solubility of the hydrophobic drug: Solubility improvement techniques can be categorized into physical modification, chemical modification of the drug substance, and other techniques.

Physical Modifications

Particle size reduction, like micronization and nanosuspension; modification of the crystal habit, like polymorphs and amorphous forms; drug dispersion in carriers like eutectic mixtures, solid dispersions, solid solutions, and cryogenic techniques.

Chemical Modifications

Change of pH, use of a buffer, derivatization, complexation, and salt formation.

Miscellaneous Methods

Supercritical fluid process, use of surfactants, solubilizers, solvency, and novel excipients.

The “core-shell structure” of the micelle facilitates its function: the core comprises the hydrophobic part of the surfactant, and the shell comprises the hydrophilic part.

However, micelles also have some disadvantages because the concept of risk versus benefit is the standardized principle used in the pharmaceutical field.

Micelles are formed using a high concentration of surfactant, which could be toxic to use.
It is susceptible to temperature changes.
When the formulation falls under CMC, the micelles disappear.
Factors affecting CMC can be amphiphile chain length, dissolved salts, head group structure, alkyl chain structure, and polar additives.

Notable Drugs that Apply the Usage of Micelles

Tamoxifen

Tamoxifen is a drug used to treat hormone receptor-positive breast cancer and to prevent breast cancer. Polymeric micelles are used to make tamoxifen more soluble in water. Tamoxifen loaded with polymeric micelles showed an increase in their water solubility.

Paclitaxel

Paclitaxel is an anti-cancer drug that is used to treat many cancers, like ovarian cancer, lung cancer, and cervical cancer. Paclitaxel is an in vitro drug (given by injection into a vein), and research has found that its effects were increased after employing mixed micelles that were made of positively charged lipids and PEG-PE.

Vitamin K

Vitamin K dietary supplements are usually sold in grocery stores and pharmacies. As vitamin K destabilizes at gastric pH, micelles are used to increase its bioavailability and protect it from degradation.

Did You Know?

Vitamin K is necessary for controlling the binding of calcium to bones and to body tissues and for the modification of proteins required for blood coagulation.

Conclusion

Micellar solubilization was and remains a major discovery in the field of solubility for poorly water-soluble drugs.

Due to its increasing adoption and use, it has proven to be a powerful alternative relevant to current applications in multiple pharmaceutical practices, such as the efficacy of drug product development in solubilizing poorly soluble drugs, reducing toxicity, and improving drug delivery by increasing bioavailability.

Furthermore, pH, temperature, hydrophobicity, buffer solutions, and volume reduction significantly affect the extent of micelle solubilization. There are many research studies on micellar dissolving in the pharmaceutical industry, promising to reveal new and advanced methods.

References

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