Biological Availability
The pharmacological technical term bioavailability is a measurement that describes the extent to which and how quickly an active ingredient is absorbed by the body and made available to the organism. Biological availability is always expressed as a percentage; the best and highest possible value is always 100 percent. However, this maximum value can usually only be achieved when drugs are administered intravenously, which in turn means that biological availability depends not only on the substance alone, but also on the formulation and the method of administration. In the case of nutrients that people consume when eating and drinking, availability also depends on the combination with other ingredients or foods. For example, coffee reduces the biological availability of many nutrients. Availability also plays a major role in cosmetics, where it is called dermal bioavailability. It describes the proportion of active ingredient that is available for biological processing after dermal and local application in the skin. However, it is somewhat more difficult to measure, since it must also be defined in which of the skin layers the respective ingredient is to reach in order to achieve a specific effect.
Biological availability in cosmetics
In principle, however, the release of active ingredients has an enormous influence on the effectiveness of a cosmetic care product. In general, there are two possibilities for substance absorption via the skin: diffusion takes place either through the skin appendages or through the horny layer. Due to the relatively small proportion of sebaceous and sweat glands as well as hair follicles, uptake via the pores usually does not play a major role. Transport through the outer epidermal layer (stratum corneum) is either transcellular or intercellular. For a long time, the transport of hydrophilic substances was classified as transcellular, but this turned out to be less likely. Meanwhile, the intercellular route is considered the definitive transport pathway for both lipophilic and hydrophilic substances.
Release and dermal bioavailability of cosmetic ingredients through the skin are determined by numerous factors and substances. Overall, the process is a very complex interplay between the respective substance and the skin. The first phase, i.e. the release of the active ingredient from the base, includes diffusion of the dissolved substance to the vehicle/stratum corneum boundary. During the subsequent penetration, i.e. the penetration into the skin, the barrier is then overcome. Subsequently, distribution into deeper epidermal layers as well as into the dermis occurs. The release is usually very rapid, while the actual penetration is considered to be the decisive speed-determining factor. The stratum corneum is a distinct barrier for the ingredients, which is partly due to its low water content. With penetration-enhancing active ingredients, biological availability can be improved or increased.
Penetration-enhancing active ingredients to improve bioavailability
Some substances are able to reversibly change the structure of the stratum corneum, i.e., they have penetration-promoting properties and contribute to better biological availability. The barrier properties of the skin decrease, while the permeability for cosmetic ingredients increases. Oleic acid is particularly worth mentioning in this context and is considered a classic penetration enhancer. Its effectiveness can even be increased by combining it with propylene glycol. Branched-chain fatty acids also have a positive effect, although the effect is not quite as strong as with oleic acid.
Other substances that improve penetration and thus also biological availability are the fatty acid ester isopropyl myristate and dimethyl sulfoxide (DMSO). The mode of action of dimethyl sulfoxide was first demonstrated as early as 1965: After DMSO was added to a cream base and an alcoholic solution, respectively, scientists observed a strong increase in the concentration of fluocinolone acetonide and hydrocortisone in the skin. The advantage of DMSO in terms of bioavailability is, among other things, its rapid efficacy, but DMSO is banned in cosmetic products in the EU.
Among the monohydric alcohols, ethanol is the most widely used as well as the best studied agent for enhanced bioavailability in terms of penetration properties. The substance is able to increase the solubility for active ingredients by penetrating into the lipid areas of the uppermost layer of the epidermis.
Urea occupies a special position among penetration enhancers. This endogenous substance assumes the function of a natural moisturizing factor in the skin. Urea effectively contributes to the hydration of the keratin material in the stratum corneum because it has a high water-binding capacity. Even in moderate concentrations (up to about three percent), it can be optimally used as a penetration enhancer.
Cosmoperine is a natural compound extracted from the black pepper plant (Piper nigrum). It is a type of alkaloid called piperine, which is the active ingredient in black pepper. Cosmoperine is known to enhance the absorption of other compounds, such as nutrients, medications, and supplements, by increasing their bioavailability. Some research suggests that cosmoperine also has other potential health benefits, such as anti-inflammatory and antioxidant effects, although further research is needed to confirm these effects.
D-panthenol, the precursor to pantothenic acid, makes the skin more permeable and therefore more receptive to active ingredients as well. More exciting information on D-panthenol can be found here.
However, a penetration-increasing effect to improve biological availability can only be expected when used over a longer period of time.
Fact sheets of the most important substances for improving bioavailability
Oleic Acid
INCI: Oleic Acid
CAS number: 112-80-1
Solubility: soluble in ethanol and methanol, insoluble in water
Boiling point: 360 degrees Celsius
Cosmoperine
INCI: Tetrahydropiperine
CAS number: 23434-88-0
Solubility: with alcohols, lipids
Melting point: 45°C
Urea
INCI: Urea
CAS number: 57-13-6
Solubility: very good in water
Melting point: 132.5 to 134.5 degrees Celsius (decomposition)
The importance of biological availability
In order to achieve an optimum active ingredient concentration as well as the best possible release of ingredients, good biological availability is of great importance. In addition, with a targeted release of active ingredients and the resulting good bioavailability, significantly fewer side effects can often be expected. We are happy to support you in the selection of suitable active ingredients and the development of efficient products.
Sources:
Skin Permeation Enhancement in Aqueous Solution: Correlation With Equilibrium Enhancer Concentration and Octanol/Water Partition Coefficient.; Li SK, Chantasart D.J Pharm Sci. 2019 Jan;108(1):350-357.
Enhancement of ketorolac tromethamine permeability through rat skin using penetration enhancers: An ex-vivo study.; Kumar P, Singh SK, Mishra DN, Girotra P.Int J Pharm Investig. 2015 Jul-Sep;5(3):142-6.
Molecular and pharmacological aspects of piperine as a potential molecule for disease prevention and management: evidence from clinical trials.; Tripathi, A.K., Ray, A.K. & Mishra, S.K. Beni-Suef Univ J Basic Appl Sci (2022) 11, 16 .