Comprehensive Formulation
The best and most effective topical products combine a variety of key ingredients, humectants and occlusives, and functional ingredients that stabilize and deliver key ingredients into the skin. Some examples are:

Key Ingredients Providing Topical Benefits
• Retinoids
• Vitamin C
• Peptides
• Antioxidants

Humectant and Occlusive Ingredients
• Glycerin
• Urea
• Natural oils
• Sodium PCA
• Hyaluronic acid
• Silicones
• Sorbitol

Functional/Carrier Ingredients
• Surfactants
• Emulsifiers
• Thickeners
• Preservatives

Using components from each of these categories to create a multifunctional formulation is critical to a product's ultimate performance, biocompatibility, delivery and stability.

Identifying Topically Beneficial Ingredients
There are several categories of ingredients that should be considered when choosing skin topicals that have been found time and again to be effective: retinoids, vitamin C, peptides and antioxidants.

Retinoids
As the vitamin A family, retinoids inhibit melanogenesis; encourage cell turnover; stimulate collagen, hyaluronic acid and elastin production; and prevent follicular impaction.
Due to its inherent instability in formation, the production of effective retinoid topicals requires the use of nitrogen blanket technology in order to minimize the raw material's contact with oxygen. Nitrogen blanket technology is highly specialized and is typically not employed by the cosmetic industry. Because of this, at least partial oxidation of the raw material occurs in formulation and prior to packaging, resulting in a less effective product altogether. Fortunately, new polymer delivery systems have been introduced that protect the raw ingredients without the need for a nitrogen blanket, making many retinoid topicals more stable and effective, while increasing products' shelf lives at the same time.

Vitamin C
L-ascorbic acid is the only form of ascorbic acid that is truly vitamin C. It is bioavailable to skin, while the esters of ascorbic acid, like ascorbyl palmitate and magnesium ascorbyl phosphate, only provide the antioxidant capabilities of ascorbic acid, not the collagen building anti-aging activity. Benefits from L-ascorbic acid:
•Stabilizes collagen;
•Encourages collagen production;
•Provides antioxidant, anti-inflammatory and UV-protection.

Peptides
A peptide is a compound consisting of two or more amino acids, the building blocks of proteins. Peptides act as neurotransmitters and hormones, providing important communication pathways in the body. There are multiple peptides available that will achieve different topical results. The following are a few examples of different peptides and their functions:
•Palmitoyl pentapeptide-4 stimulates dermal fibronectin and collagen types I and III;
•Palmitoyl oligopeptide stimulates dermal fibroblast production;
•Acetyl hexapeptide-8 prevents dynamic wrinkling by inhibiting repetitive motions.

Antioxidants
Antioxidants are molecules that are able to slow or prevent the oxidation of other molecules. Oxidation produces free radicals, which trigger a chain reaction in the body that damages cells. Antioxidants exist in three forms:
•Primary antioxidants – donate electrons and disarm free radicals;
•Secondary antioxidants – chelate metal ions and remove radical initiators;
•Co-antioxidants – facilitate antioxidant action of other compounds;
•Some ingredients function as several forms of antioxidant.

Some antioxidant examples are: L-ascorbic acid, tea polyphenols, resveratrol, glutathione and vitamin E, which donate electrons to damaged, unstable cells in the skin. Silybin acts by chelating damaging metal ions from negatively affected cells. Sustained protection against product oxidation additionally comes from the co-antioxidants L-ascorbic acid, vitamin E and glutathione, as they protect, support and aid in the regeneration of one another.

Science and Stability
To ensure the overall efficacy of a selected product, it is important for clinicians to ensure the product's ingredients have been backed by science. Many of these ingredients have been on the market for decades and have gone through rigorous testing to substantiate their benefit to the patient. This is counter to newer ingredients that claim to provide drastic results, despite not having gone through the research necessary to validate these purported results.
In addition to scientific validation, a product needs to contain stable key ingredients. Since more than a few of the time-tested topical actives are inherently unstable in formulation, utilizing stabilization technology in a formulation is critical. There are several raw material stabilization
systems available.
•Encapsulation into lipids, microcapsules or liposomes;
•Micronization (creating smaller particles of an ingredient);
•Esterfication, a process that binds one molecule to another.

Encapsulation, or the use of a protective casing to shield key ingredients from air, water or light, is the method of stabilization considered by many to be the most effective. The casings allow the ingredients to remain in their most active forms, while being easily broken down upon contact with the skin or other forms of manipulation, releasing those active elements.
For example, L-ascorbic acid is water-soluble and susceptible to oxidation. If formulated in a water-based product, it is allowed to become unstable, with a shelf life typically not surpassing a single year. Anhydrous (water-free) bases suspend the L-ascorbic acid and allow it to remain stable and protected until use, and provide a substantially longer shelf life for the finished product. Removing water from the equation allows L-ascorbic acid to preserve its efficacy. The use of opaque material packaging and limited oxygen contact through airless containers or nasal-tipped orifices help extend product shelf life as well.
Micronization is the process by which an ingredient is broken down in to smaller particles making it more stable and more easily absorbed into the skin.
Esterification is the process of binding two molecules to one another to stave off breakdown. In some instances it can make substances more stable and easily release them into the skin, while other times it can make an ingredient ineffective. In the case of tocopheryl acetate (tocopherol and acetic acid), the esterified molecule is more stable and once it is applied to the skin, the molecule cleaves, freeing the vitamin E to become an active antioxidant on the patient's skin. On the other hand, when L-ascorbic acid is combined with palmitic acid through esterification to create ascorbyl palmitate, there is no mechanism within the skin to free the L-ascorbic acid. In cases like this, the ester forms have reduced efficacy.
There is also synergistic activity to consider. The formulation of multiple, complementary ingredients that protect one another from breaking down enhances shelf life and efficacy. For example, when L-ascorbic acid and vitamin E are formulated together, each ingredient replenishes the activity of the other, enhancing the stability of both ingredients.
Finally, formulations as a whole must also remain stable for their intended shelf life. For treatments that are water-based, a preservative element is essential to protect patients and prevent bacteria, yeast or mold from forming. Also, the oxidation of a product could lead to a loss of efficacy by altering the ingredients' molecules. If a product oxidizes prior to interaction with the skin, it will become less effective.

Delivering Benefits
Even if a formulation uses a scientifically proven key ingredient or group of ingredients, an effective delivery system must be employed to ensure they reach their intended target to produce the desired dermal outcomes. Some vehicles for delivery include: emulsions, suspensions and gels.
Emulsions are creamy in consistency and ensure the active components of the product will be evenly distributed throughout the formulation, and in both the skin's aqueous and lipid environments. Emulsions can combine water-soluble and oil-soluble ingredients. They are generally used for moisturizers as opposed to corrective topicals due to their thick consistency potentially impeding the penetration of key ingredients into the skin.
Suspensions are liquid in form and usually experience a separation of ingredients, requiring the agitation of the bottle prior to use to ensure redistribution of all components. Oftentimes suspensions are used when the ingredients of a product will not dissolve when mixed with water or oil, such as in cleansers.
Gels can be either water-soluble or oil-soluble, appearing as transparent, semi-liquids. Gel delivery systems are often used for serum products. Gel bases are used commonly for corrective products, as they are thinner than emulsions and suspensions, allowing them to penetrate the skin more easily.
Stabilizing and preservation of each of these vehicles is also important to be certain the key ingredients in a product's formulation are not broken down and to prevent the growth of any abnormal microbials within the product.
Rather than pursuing a miracle ingredient that is likely not on the horizon, rely on time-tested and scientifically substantiated actives that are well-formulated to ensure efficacy, stability and optimal delivery. These are the formulations that will ultimately provide your patients with the healthy, beautiful skin they seek.

Ivana Veljkovic, Ph.D., manages product development, regulatory and clinical trials for PCA Skin®. She received her doctorate in organic chemistry from Freie Universität Berlin, and her master's of science degree in chemistry from the University of Belgrade in Yugoslavia. Veljkovic has previously worked as a research scientist specializing in the synthesis and purification of organic compounds before joining a health care company in Canada that represented PCA Skin®. In her role, she worked directly with physicians, nurses and aestheticians, educating them about skin physiology, ingredients and proper treatments for specific skin conditions.