Cosmeceutical Formulation Considerations

Published on 15/03/2015 by admin

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Chapter 3 Cosmeceutical Formulation Considerations

INTRODUCTION

The current success of efficacious skin care formulations, commonly referred to as ‘cosmeceutical’ products, offers the cosmetic chemist tremendous challenges and opportunities. These challenges and opportunities have resulted in the introduction of new and unique formulations that are intended not only to address the aesthetic aspects that consumers desire (application, feel, smell, etc.), but also to maximize the performance of the product. The formulations are now an integral part of the delivery systems that are intended to maximize performance and provide consumer-perceivable benefits.

This chapter discusses current vehicle trends, delivery systems, and formulation parameters that have become an integral part of cosmeceutical products.

VEHICLES

The primary purpose of the vehicle is to optimize the delivery of ‘cosmeceutical’ benefits to the consumer. These usually involve providing immediate or short-term benefits as well as benefits that take 30–60 days to manifest. All this is done while insuring that the formulations are safe for use as well as preserved against potential microbial contamination.

The most common, and still the most efficacious, vehicle is the emulsion. However, this category has seen tremendous growth by the inclusion of silicone-in-water emulsions, water-in-silicone emulsions, and nonaqueous emulsions that use oils/silicones in combination with glycols or other polyols. The increased use of silicones has expanded the types of formulation being introduced, resulting in an increase in products that are now referred to as ‘serums’. A serum, like a ‘lotion’ or a ‘cream’, has no legal definition but has become associated with formulations that are generally low-viscosity translucent liquids. They are frequently used in eye treatment products and specialty applications to the face (i.e. spot treatments etc.).

In the previous chapter on this subject, written by my colleague and friend, Ken Klein, he described what constitutes an oil-in-water emulsion (O/W), water-in-oil emulsion (W/O), liquid crystal stabilized emulsions, and multiphase emulsions (W/O/W). We are going to expand on that and include some of the current formulation trends in these categories.

• Emulsions

OIL-IN-WATER EMULSIONS

The challenges that are present in the current development of oil-in-water (O/W) emulsions are the increased use of silicone and silicone polymers in these types of formulation. Generally speaking, many of the silicone ‘oils’, polymers and elastomers have very poor compatibility with typical organic ‘oils’ or esters. The challenge is in the selection of the emulsifier system and the combination of hydrophobic materials that will allow for a homogeneous and uniform internal oil phase. In addition, this phase is also a delivery system for a number of functional ‘active’ ingredients, enhancing their functionality and performance.

The choice of ingredients now needs to consider the effect on performance as well as aesthetics. Figure 3.1 is an O/W emulsion in which the predominant components of the oil phase are a blend of silicones. This emulsion can be modified with the addition of bioactive ingredients—antioxidants and skin-soothing ingredients. The other aspect of this formulation that is worth noting is the use of an emulsion-stabilizing system that can be added at the end. This ingredient serves a dual function—adjusting viscosity and improving emulsion stability. Care must be taken, however, because these emulsion-stabilizing systems can also affect the feel of the product.

Fig. 3.1 An oil-in-water (O/W) emulsion

WATER-IN-OIL AND WATER-IN-SILICONE EMULSIONS

Water-in-oil (W/O) and water-in-silicone (W/S) emulsions, sometimes referred to as ‘inverse emulsions’, are formulations in which the internal or dispersed phase is a water phase, and the oil (or silicone) phase is the continuous or external phase. While still much less popular than O/W emulsions, recent advances in silicone-based emulsifier systems have caused an increase interest in these types of formulation. The formulation from Dow Corning (Fig. 3.2) demonstrates the use of these newer emulsifier systems. They have become increasingly useful when developing water-resistant sunscreen products and when looking to incorporate more lipophilic (oil-loving) functional materials into formulations that deliver skin care benefits such as barrier protection. The formulation of ‘inverse emulsions’ has been extended to where the internal phase is a hydrophilic polyol in place of water. The formulation from Momentive (Fig. 3.3) is an example of an ‘anhydrous’ emulsion which can be used as a delivery system for cosmeceutical ‘actives’ that have stability issues in water (i.e. ascorbic acid—vitamin C).

Fig. 3.2 Emulsifier system

Fig. 3.3 An anhydrous emulsion.

(Reproduced with permission from Momentive, Wilton, CT.)

DELIVERY SYSTEMS

The success of ‘cosmeceutical’ formulations is dependent on two very critical factors—the aesthetics of the formulation and the performance of the products. The aesthetics (color, odor, feel, application, etc.) are the properties of a formulation that will determine whether the consumer will continue to use the formulation as directed. If the consumer does not ‘like’ the product, she (and, as of this writing it still is primarily women who use ‘cosmeceutical’ skin care products) will not use it. As with any skin care or topical treatment the results will only be obtained with regular use of the product.

Performance and delivery of the claimed benefits are the second part of the equation. To maximize the performance of the products, and to deliver the claimed benefits in the shortest period of time, formulators have started to look at enhanced delivery systems. Delivery systems also serve to protect cosmeceutical ‘actives’ and help with product and ingredient stability. We will review several of these types of delivery system and discuss the ways they enhance the performance of the ‘cosmeceutical formulation’.

• Polymeric entrapment systems

Frequently referred to as ‘microsponge’ entrapment systems, these polymeric systems can be visualized as a sponge with a very high internal volume that allows for entrapping up to 50% of hydrophilic (water-loving) or lipophilic (oil-loving) materials. The primary release mechanism is diffusion, in which the entrapped material slowly diffuses out from the polymer. This allows for a time release of materials so that the benefits can be extended over a longer period of time, rather than getting a ‘bolus’ effect where the entire ‘active’ is released all at once. Entrapment systems can also extend the stability and protect ‘functional’ materials that have a tendency to degrade, such as retinol and benzoyl peroxide. One of the polymer systems used is allyl methacrylate copolymers. Because of their microsponge nature they can also provide oil-absorbing benefits when applied to the skin.

• Micropatch™ delivery system

This BASF system is made up of a network of naturally derived macromolecules that can entrap functional materials and deliver them to the skin. It is a ‘virtual patch’ whose primary function is to deliver long-lasting moisturization to the skin. While helping to maintain skin hydration, which is essential to the proper functioning of the skin’s barrier properties, the Micropatch™ also functions as a delivery system for other cosmeceutical actives such as caffeine (for cellulite treatment). As with polymer entrapment, this delivery system functions primarily on the surface of the skin by preventing water loss and delivering ingredients to the skin.

• Liposomes and other nano delivery systems

We are all familiar with liposomes. They are microscopic spherical vesicles that are formed when phospholipids are hydrated. Typically, liposomes are 200–800 nm in size. They are designed to entrap and deliver into the skin both hydrophilic and lipophilic ingredients. The core of a liposome contains water-soluble material and the ‘wall’ that makes up the liposome contains oil-soluble ingredients. Nano particles are liposomal structures in which the lipophilic material is entrapped in the core and the hydrophilic material is entrapped in the ‘walls’ (Fig. 3.4). The primary issue with liposomes, much less than with nano particles, is that they are very sensitive vesicles that can be destroyed by a number of factors (e.g. pH, type of emulsifier used, solvents, etc.), but, because their structure is very compatible with the lipid composition of the skin and with cell membranes, they are excellent transdermal delivery systems.

Fig. 3.4 Liposome structure

Delivery systems function to protect, isolate, and effect delivery of materials to the skin. There are even delivery systems that are intended to prevent materials from penetrating the skin, such as ultraviolet (UV) radiation absorbers. An Israeli company called Sol-Gel Ltd has a product line called UV-Pearls™ which contain high concentrations of US Food and Drug Administration (FDA)-approved sunscreens in a transparent non-‘leachable’ silica micro-shell. The claimed benefits are improved UV stability and keeping the sunscreen actives on the top layers of the skin where they are most effective in providing UV protection.

ADDITIONAL FORMULATION CONSIDERATIONS WHEN DEVELOPING COSMECEUTICAL PRODUCTS

Cosmeceutical formulations are becoming more complex and the activity and stability of many of the functional ingredients being used need to be considered.

• pH

The pH of your formulation can be critical to the functionality of the product. For example, if a formulation is intended to be an exfoliating product that contains either an alpha-hydroxy acid (AHA) or an enzyme, the pH is critical to the performance and the stability. In order for an AHA formulation to be effective and safe the pH should be 3.5–4.5. Above this range will compromise performance and lower than this will compromise safety/irritation. Enzymes should also have a slightly acid to neutral pH in order to maintain their stability. The color and odor of many materials will be affected by the pH environment in which they are used.

• Temperature

Since most cosmetic emulsions are produced at elevated temperatures (70–75°C), the temperature stability of the functional materials should be known so that they can be incorporated in their proper place in the manufacturing process.

• Solubility

While this may seem the most obvious attribute to consider, the effectiveness and the availability of a cosmeceutical ‘active’ can be altered depending upon the phase to which it is added when making the formulation. Knowing the solubility of the functional ingredients being used is very important.

• Compatibility

More and more cosmeceutical products are using ‘cocktails’ of functional ingredients to provide the desired skin care benefits. The combination of materials must be compatible with each other as well as with the other ingredients in the formulation. In many cases you only find out about these incompatibilities after you make the formulation and subject it to accelerated stability testing. In addition, when working with ‘cocktails’ of materials, make sure that they are all functional within the parameters of the formulation. If a component only works at pH 7.0 or higher and the pH of your formulation is 5–6, you may not be maximizing the benefits that are to be obtained from using that material.

• Preservation considerations

All aqueous-based formulations are subject to microbial contamination, not just during manufacturing but more importantly during consumer use. Care must be taken to insure that these formulations are adequately preserved. This has become a challenging area, since many preservatives are not being used because of safety concerns (real or imagined) and some are not allowed in some international markets. The pH of the formulation needs to be considered when selecting a preservative. Preservatives such as ‘sorbates’ and ‘benzoates’ only work when the pH of the formulation is < 5.0.

It is recommended, wherever possible, that a salt of ethylenediaminetetraacetic acid (EDTA) be used. While this is frequently, and mistakenly, referred to as a preservative, it is not. Its function as part of the preservative system is to weaken the cell walls of bacteria and make them more susceptible to various antimicrobial agents being used. EDTA salts are commonly used at 0.05–0.2% in formulations. The test that is used to determine preservative efficacy is called a preservative challenge test. The test protocol involves inoculating a product with bacteria (Gram positive and Gram negative), mold, and yeast, and determining how long it takes the preservative system to remove essentially all these contaminants from the formulation.

• UV absorbers and antioxidants

These ingredients should be considered in cosmeceutical formulations not only because of the skin benefit claims that can be made, but also because they can play a significant role in helping maintain product stability, especially color and odor. In the area of UV protection for the product the choice of materials is much broader than the UV absorbers that are approved by the US FDA as sunscreen actives.

• Cost

This category has been included because it is a key area that needs to be addressed when selecting cosmeceutical ‘actives’. The cost contribution that ingredients provide to the formulation is based on the raw material cost and the percentage used. No matter what the ultimate selling price of the finished cosmeceutical, the cost of the product (of which the raw materials usually contribute no more than 5–10% of the retail selling price) is an area that must be kept in mind when formulating the finished product.

• Stability considerations

When formulating drug products in the US, an expiration date is required unless the product has a proven shelf-life of at least 3 years. Since cosmeceuticals are cosmetics and not drugs, no expiration dating is required. However, many skin care products are combining drug claims along with ‘cosmeceutical’ benefits. These products include, but are not limited to, skin protectants, sunscreens, acne products, and skin whitening products. In these cases the stability rules for drugs must be followed.

In order to claim a 2-year expiration dating on your product the FDA has accepted specific accelerated stability testing so that drug products can be marketed while the full 2-year stability testing is conducted. What the FDA is concerned with is that the drug active is maintained in the formulation at +10% of the labeled claimed amount. The aesthetic integrity of the formulation is not of concern to the FDA and stability testing that determines this should also be conducted. This will insure that the product as sold to consumers is suitable for use. While it is difficult to predict long-term stability, given the myriad of possible storage conditions, many companies have developed testing that has been shown to be quite effective in judging shelf stability.

Stability testing protocols can vary with products stored at various temperatures to determine in as short a time as possible the long-term integrity of the product. It has been suggested that if a product is stored at 45°C for a period of 90 days, and no product degradation is seen, it is likely that the product will exhibit a shelf-life of at least 2 years. In some cases the product is stored for 1 month at 50°C as a more rapid test to predict shelf-life. The problem with this storage temperature is that in many cases materials used in the formulation, including the emulsifying system, can show stability issues simply because of the temperature—50°C stability will give you a ‘yes’ and will not necessarily give you a ‘no’ result. If a product is stable for 1 month at 50°C it is a very good indication that it will have good long-term shelf stability. If the product shows stability issues after 1 month at 50°C it may be because of the temperature and not be indicative of shelf-life.

Some typical storage conditions used in product stability testing are:

37°C: 120 days

40°C/70% relative humidity: 90 days (drug stability testing conditions)

Freeze/thaw (−10°C to 20°C): 3 cycles (24 hours at each temperature)

Exposure to sunlight: 3 months.

All stability testing must be conducted in both glass and the commercial packaging. In addition to looking for signs of physical instability, consideration should be given to the following factors:

Appearance/odor/color (compared to a refrigerated (4°C) sample)

Particle size change (for emulsions)

Weight loss (in the commercial package) not to exceed 1% per month when stored at 45°C

Percentage of drug actives (if product is an over-the-counter drug)

Percentage of preservatives

Percentage of cosmeceutical actives.

SUMMARY

The challenges facing the cosmetic chemist in developing state-of-the-art cosmeceutical formulations are becoming increasingly complex. In addition to knowing the basics of formulating emulsions, gels, liquids, etc., the cosmetic chemist has had to learn areas such as ‘bioactivity’, ‘mode of action’, ‘percutaneous absorption’, etc. so that the best materials for the formulations being developed are selected. A quality, stable, efficacious cosmeceutical formulation involves the development of the base and the optimization of the functional ingredients that are used to provide the immediate and long-term benefits demanded by the consumer. The choice of vehicle, the selection of a suitable delivery system, and the ability to make sure that all the aspects of the formulation go together has resulted in the realization that formula optimization has become an integral part of the development process leading to the creation of the cosmeceutical formulations that consumers require.

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