Are the Actives in Formulations Really Active?

Conventionally the term actives are used for the ingredients that actually work in Over the Counter drugs (OTC) or pharmaceutical formulations and are regulated by an appropriate regulatory authority like FDA in the US. However, in skin or hair care formulations, any ingredient that performs a specific action and exerts beneficial effects to resolve targeted issues or enhance an individual's well-being is referred to as “Actives”.

A single formulation is constituted by one or multiple actives and all other components (like excipients in pharmaceutics) necessary for delivering the active, enhancing its functionality or efficacy along with stabilization effects. In the context of skin care formulations, the most common actives which are hailed as a holy grail for healthy skin include but are not limited to Retinoids, Hyaluronic acid, L-ascorbic acid, Resveratrol, Niacinamide, Alpha-hydroxy acids (Glycolic acid, Citric acid, Lactic acid), Beta-hydroxy acids (Salicylic acid), Ceramides, Hydroquinone, etc.

Nevertheless, formulating an effective and standout product requires not only expertise in the selection of every active, excipient, or preservative ingredient but also precision in achieving the right concentration and combination of the constituents. Though there are several factors to be considered for getting the intended potency and safety of the product, let’s look at the common fallacies which hamper achieving the intended results.

Lack of solubility will separate the active armor from the intended action plan

Various factors decide the solubility of active, including its hydrophobic or hydrophilic nature, molecular weight, pH, temperature, and other constituents used in the formulation. So, any issues with incorrect selection of constituents or non-compliance with the desired solubilizing environment can lead to precipitation of active.

For instance, Salicylic used in numerous skincare products can precipitate out due to it's poor water solubility, resulting in a gritty texture in the final product.

Problems with Permeability will never let it through your skin to act

The human skin is a complex line of defense and active molecules need to transverse through it to the intended site of action for achieving the intended purpose. If the nature of the active is not compatible with the base of the formulation or is unable to cross through the epidermis, lathering it onto the skin will be of no use.

For example, collagen is very popularly touted as a magical solution to remove fine lines, and wrinkles and infuse firmness. However, being a protein its molecular size makes it too large to penetrate the stratum corneum, and thus, its topical application in native form isn’t likely to yield any benefit.

Combining incompatible ingredients is a recipe for an ineffective cocktail

For differentiating a product for its efficacy, the synergistic combination of the right actives can be a game changer. However, the reverse also stands true as mixing incompatible ingredients will not only fail to enhance the potency but might also inhibit the individual effect.

For instance, incorporating Vitamin C in sunscreens or Vitamin E serums can amplify the antioxidant ammunition and enhance protection against photoaging or other free radicals-induced oxidative damage. However, combining Vitamin C with alpha-hydroxy acids or salicylic acid, or retinol in a formulation can reduce the efficacy of all the constituting ingredients due to compatibility issues.

Similarly, combining Retinoids or hydroquinone with Benzoyl peroxide will ensure neither will work optimally except for being highly irritating to the skin. Another relevant example is the incompatibility of Cetearyl alcohol and Ceteareth-20, both of which are highly popular and safe ingredients in skin care formulations but when combined, the formulation can be comedogenic.

The arithmetic of more the concentration, better the efficacy doesn’t work in skin science

The approach of chasing a high percentage of actives for enhancing potency does not work for all skincare formulations. It is imperative to understand that choosing the optimal concentration of active ingredients is very critical for achieving potency along with ensuring safety. Though it is somewhat obvious that an overdiluted formulation will not achieve the desired results, packaging formulations with above optimal concentrations will either lead to unnecessary drainage of resources or loss of efficacy with adverse reactions.

For instance, formulating a 30% Vitamin C serum without the right stabilizers and additives will only lead to loss of its stability and skin irritation. Similarly, loading actives in sunscreen to formulate an SPF of more than 100 does not offer absolute foolproof protection from the sun but increases the chances of breakouts/irritation and increased risk of UV damage due to complacency towards reapplication.

Small variations in pH formulations can lead to big non-functional issues

It has been well established that topical formulations in the lower pH range (4.0-6.0) are more compatible for crossing the skin barrier and exhibiting desired product activity. However, the optimal pH of the active ingredients of the formulations might not be in sync with this range, limiting their efficacy on the skin.

For instance, many formulations like that of Vitamin C as well as Alpha Hydroxy Acids, require optimal pH of less than 4 to show maximal potency, but functionality at that acidic range will cause sensitivity or irritation to the skin. The delicate pH conundrum can get more perplexing in cases like those of salicylic acid (pKa~2.97), wherein formulations with high pH will not be effective in penetrating through the skin barrier as it will exist in deprotonated less active form.

Relying on conventional W/O or O/W emulsions in gels, and lotions with free actives is not the best way forward

Generally, most of the actives in their native free form suffer from many limitations of low permeability, high instability, unregulated release, etc. Further, free active molecules can also interact with other ingredients in the formulation to generate unintended side effects. For instance, Retinol degrades quickly on exposure to light and hence, encapsulating it in novel delivery systems can help to retain its efficacy to achieve the desired effect.

Overall, formulating potent actives with sustained efficacy and stable shelf-life is a challenging task that requires thorough expertise, precision, and targeting of multiple etiologies with synergistically acting compatible ingredients.