INTRODUCTION:

For many centuries, man has made attempts to artificially color, bleach and in other ways alter the normal appearance of his skin. These practices have been intimately intertwined with his philosophy, his beliefs, religious and otherwise and his insatiable vanity. Juices, plants and fruits particularly of the citrus variety, have long been held to exert a lightening or bleaching effect on the dark skin, lemon juice being one of the remaining ''hangers-on''. In this category, any number of compounds have been used over the ages to achieve a bleaching effect, prominent among them are such agent as ammoniated mercury and hydroquinone bleaches. Contemporary Western man sometimes desires skin colour alteration to make dark skin lighter and light skin darker. Regardless of this idiosyncrasy, most of the people also desire to slow down the ageing process of skin to have youthful and glowing skin. For this reason, attempts are made to lighten areas of excessive pigmentation.

Motives behind the use of skin lightening products vary considerably between cultures. In Western countries, people wish to eliminate or inhibit the development of irregular pigmentation including melasma (chloasma or localized discoloration), age spots (Lentigo senilis) or liver spots (associated with sun damage or aging sometimes appearing as raised spots or Seborrheic keratoses) and freckles (Lentigo aestiva). In Asia, a lighter skin colour is associated with beauty and aristocracy. Therefore, in Asian countries, skin lightening products are used with the intent to lighten and brighten the skin tone. Especially if depth of color is more pronounced than that of surrounding area. Conversely, the same effect could be achieved by darkening areas showing less pigmentation than the surrounding area.^[1]

Physiology and chemistry of pigmentation and ageing:

It is necessary to know something about factors affecting skin colour, particularly its process of pigmentation, before one can fully understand the indications for the mechanism of agents. For example, the colour of the skin is affected to a large extent by the state of its blood circulation. In addition, the exterior horny layer, keratin, which is dead protein substance, has an indigenous color and can alter skin appearance depending on its thickness. Exposure to the element may produce thickening to the extent that the normal color is altered or dulled.^[2]

As we age, the dermis decreases in thickness by about 20%.As for it thins it loses vascularity, cellularity and sensitivity. Its ability to exchange or retain internal heat is diminished. The skin becomes thin, fragile and slow to heal. Sweat and sebaceous glands are reduced both in number and effectiveness. Sensory neurons are decreased by 30%. Many factors, both extrinsic and intrinsic, cause the skin to age. Those causes can easily be divided into three main categories: biological aging, environmental aging, and mechanical aging. Aging is thus the result of a genetic program or a clock that is implanted in the genetic make-up of each species. One must also remember that cumulative damage to the genes and proteins derived thereof, result in compromised function and homeostatic failure. This leads the organism towards premature aging and death, which in turn shall depend on its repair systems.^[2]

Let's look at each cause individually to understand ways they can be minimized. The first category is biological aging. Biological aging is the result of changes—often genetically determined—that occur naturally within the body. Everyone has a biological clock or chronological age determined by genetic makeup. This applies to the skin as well. As our biological clock ticks, our skin gradually loses its ability to function as it once did. Biological aging occurs as a result of natural changes within the body that manifest themselves in outward signs of aging on the skin. Frequently, changes associated with biological aging are the result of a gradual shift in the balance of certain hormones and messenger molecules excreted by other glands and organs within the body. Many of these changes are genetically determined and cannot be stopped.^[2]

Fortunately, some of the factors contributing to biological aging can be controlled. Scientists are beginning to understand how free radicals (unstable molecules) damage proteins, lipids, and the DNA within cells, and, in turn, accelerate the biological aging process. Antioxidants are molecules with the ability to neutralize free radicals in the skin. A healthful diet full of antioxidant-rich fruits and vegetables, along with nutritional supplementation and topical application of key nutrients, may help decrease the intensity and delay the onset of many changes that are a result of biological aging.^[2]

The second category of factors that cause the skin to age are all results of extrinsic sources in the environment. Environmental aging occurs as a result of daily exposure to trillions of free radicals from a variety of sources: the sun's ultraviolet rays, pollution, smoke, harsh weather, and external stress. These free radicals damage lipids, proteins, and DNA, all of which limit the ability of cells to function and cripple the integrity of overall cell composition. Years of accumulated environmental stress on cellular structures results in the premature aging of the skin.^[2]

Sun exposure is the primary environmental stressor leading to damaged skin. The damage to skin components caused by both prolonged and incidental sun exposure is called photoaging. Although cigarette smoke, exposure to harsh weather conditions, and pollution are prolific contributors to environmental aging, UV damage from the sun's rays accounts for 90 percent of premature skin aging. Photo aging damages collagen, elastin, melanocytes, and the moisture barrier, resulting in wrinkles, sagging, uneven skin tone, dark spots, and a rough, dry skin texture.^[2]

While sun exposure is the environmental stressor that accounts for most premature skin aging, there are others. Pollution damages skin by increasing free radical production and increasing the effects of UV radiation. Harsh weather (dry air, wind, and cold) depletes skin of essential moisture, resulting in a rough texture and fine, dry lines. Cigarette smoke increases free radical production and may decrease collagen and elastin production. Cigarettes also significantly decrease the supply of oxygen to skin cells.^[2]

The third category of aging is called mechanical aging. Mechanical aging is the result of continually repeated wrinkle causing behaviours, muscle movements repeated day after day and year after year. Although it is unrealistic to avoid some wrinkle causing behaviors such as smiling and frowning, the following behaviours should be avoided to help prevent premature signs of mechanical aging:

1 Squinting.

2 The thinker stance (resting chin or cheek in the hand).

3 Sleeping on your side or stomach.

4 Scrubbing with hot water.

5 Weight fluctuation.

6 Unbalanced diet and lack of sleep.

7 Pursing the lips while smoking or drinking from a straw^[2].

Overview of melanin:

Skin complexion is a characteristic that is affected by many factors. Various genes, nutrition, and environmental factors can play a role in the colour of skin. One of the most notable components of skin that contributes to complexion is a pigment known as melanin. In the skin, melanocytes are situated on the basal layer which separates dermis and epidermis. The melanin may be overproduced with chronic sun exposure resulting in malignant melanoma or other hyperpigmentation diseases.^[3]One melanocyte is surrounded by approximately 36 keratinocytes. Together, they form the so-called epidermal melanin unit.^[4]Let's discuss melanin and its functions in humans and other animals. Melanin is the cytochrome pigment whose light absorption and scattering properties impart colour to the human pupil, iris, skin, and hair.

Fig.1: Structure of Skin^[5]

Functions:

Melanin is a pigment that is produced by cells known as melanocytes in the skin of most animals, including humans. This pigment comes in different shades, depending on the genetic makeup of the individual. Melanin comes in two basic forms and can range from yellowish-red to dark brown. Eumelanin is the most common form of melanin and is brownish in colour. The other basic form is called pheomelanin, which produces reddish-brown colour that is often associated with freckles and red hair. The production of melanin in the individual is determined by several factors.^[6]

Genetically speaking, every individual on Earth has approximately the same number of melanocytes. The difference, then, in the production of melanin is affected by:

Exposure to UV radiation: Melanin is produced as a response to UV radiation in order to prevent damage to the DNA in the integument. Individuals, who are exposed to UV light, such as the sun, will produce more melanin for protection.

Genetic makeup: Different ethnicities and cultures are genetically pre-disposed to producing particular shades and amounts of melanin due to inheritance. This is, essentially, one of the primary indicators used in determining race in the human population. It is important to note that this is, and has historically been, a controversial form of human identification

Size of melanocytes: Melanocyte size varies in different individuals and may lead to a difference in the amount of melanin produced per cell. The lack of melanin and its consequences, when we have low melanin in the body the consequences are visible, a lack of extreme melanin occurs in the form of albinism, however, a considerable deficiency of it can also manifest as vitiligo, a condition that can reduce the existing pigment in certain areas of the body.^[7]

In addition, a lack of considerable melanin in the epidermis can cause the early appearance of gray hair, while its excess can trigger the appearance of age spots.

Production of melanin:

Upon exposure to UV radiation, DNA damage triggers cytokines, growth factors and other inflammatory factors to stimulate melanin production. Melanin is produced by melanocytes situated in the basal layer of the epidermis. The melanocortin 1 receptor (MC1R) is regulating the production of both eumelanin and pheomelanin, and the gene encoding MC1R has been sequenced from different ethnic groups. Both types of melanin are synthesized from tyrosine by hydroxylation to dihydroxyphenylalanine (DOPA) and subsequent oxidation to dopaquinone; both reactions are catalyzed by the enzyme tyrosinase, which is the rate limiting step. Differences in levels of melanin production is being differentiated by the different skin types and in vitro cultures of melanocytes obtained from black skin donors produces higher levels of melanin where compared to those obtained from Caucasian skin. However, the level of tyrosinase was found to be equal in the different skin type.^[8]

The melanocytes, by increasing the production of intracellular nitric oxide (NO), they trigger signal transduction cascades to initiate melanogenesis through a series of oxidative reactions involving the amino acid tyrosine in the presence of the enzyme tyrosinase. Even this leads to the production of melanin. Melanin granules synthesized in the melanocytes are then transferred from the cytoplasm of the melanocytes to the basal cytoplasm of the keratinocytes. In the human epidermis, melanocytes work in close harmony with their neighbouring cells such as keratinocytes via their dendrites. They thus form a protective covering in the inner layers of the epidermis, absorbing UV rays and inhibiting their penetration.

Eumelanin:

Firstly, dopaquinone is converted to leucodopachrome and then dopachrome through auto-oxidation, and subsequently in the presence of dopachrome tautomerase and dihydroxyindole-2-carboxylic acid oxidase, dopachrome is converted to 5, 6-dihydroxyindole. Finally, the oxidation of 5, 6-dihydroxyindole (DHI) to indole-5,6-quinone by tyrosinase leads to the formation of eumelanin (brown-black pigment).

Pheomelanin:

In the presence of cysteine or glutathione, dopaquinone is converted to cysteinyl dopa Subsequently, pheomelanin, a yellow-red pigment, is formed through the oxidative polymerization of cysteinyldopa via 1, 4-benzothiazinylalanine intermediates.

The Fitzpatrick Classification Scale:

Aka Fitzpatrick skin typing test or Fitzpatrick phototyping scalewas developed in 1975 by Harvard Medical School dermatologist, Thomas Fitzpatrick, MD, PhD. The Fitzpatrick Scale is a numerical classification schema for skin typing. This scale classifies person's complexion and their tolerance to sunlight and UV radiation. The Fitzpatrick skin type does not change. Fitzpatrick type is something people are born with and will die with. Only the degree of tan can change.It remains a recognized tool for dermatologic research into the color of skin and is also used to aid practitioners in the care of their patients. ^[6]

Fig.2: Melanogenesis^[8]

Chemical tyrosinase inhibitor:

The inhibition of tyrosinase is the most widely reported screening method in the literature for skin-lightening ingredients. Tyrosinase is a copper-containing enzyme present in melanocytes that catalyzes the production of melanin. The biosynthetic pathway of melanin synthesis was ﬁrst elucidated by Raper. Tyrosinase inhibition may be achieved by inhibitors from chemical orbiologicalsources.^[9]There has been tremendous activity in the identiﬁcation of tyrosinase inhibitors that are of synthetic origin. Such compounds are generally highly pure and potent. Synthetic compounds of various classes like hydroquinone and derivatives, phenolic amines, coumarins, chalcone analogs, hydroxy stilbene derivatives, benzaldehyde analogs, biphenyls, and trihydroxy ﬂavones have been studied for their tyrosinase inhibitory properties.^[10]

Hydroquinone:

Hydroquinone is chemically (1, 4-dihydroxybenzene) phenolic compound having chemical formula. It is a watersoluble reducing agent which is used widely in topical skin creams. It acts as a depigmenting agent by inhibiting melanogenesis. It is useful in the treatment of dyschromias (melasma), contact vitiligo, post inflammatory hyper pigmentation (PIH), seborrheic dermatitis and exogenous ochronosisetc.^[11] It is one of the important agents when treating PIH. It is a compound which inhibits tyrosinase, thereby reducing the conversion of dihydroxyphenylalanine (DOPA) to melanin [5]. In the US, hydroquinone is available over the counter (OTC) at 2% and in a prescription strength from 3% to 10%, although hydroquinone is typically used at 2–4% concentrations. Chronic, unsupervised use of hydroquinone could result in a hyperpigmented, skin-altering condition called exogenous Ochronosis^[12]Hydroquinone covalently binds to histidine or interacts with copper at the active site of tyrosinase.^[13]

Kojic Acid:

Kojic acid has recently been used as a 2% cream, alone or in combination with glycolic acid or hydroquinone, due to its inhibitory action on tyrosinase. It was found that kojic acid, which is used in cosmetics for its excellent whitening effect, inhibits catecholase activity of tyrosinase in a non-classical manner.^[14] In a comparative study in Chinese women with epidermal melasma, half of the face was treated with kojic acid 2% gel plus glycolic acid 10% and hydroquinone 2%, and the other half of the face with just glycolic acid 10% and hydroquinone 2% better results were obtained on the half of the face treated with the cream including kojic acid. A common adverse effect with kojic acid use is contact dermatitis.^[15]Although kojic acid had been widely used in skin care products in Japan, more recent clinical studies conducted there have demonstrated its highly sensitizing potential.^[22] Kojic acid has also been recently banned from the Japanese market over mutagenicity concerns.^[16]

Arbutin:

Arbutin, a naturally occurring beta-D-glucopyranoside of hydroquinone, Arbutin is derived from the leaves of bearberry, cranberry, mulberry or blueberry shrubs, and also is present in most types of pears is effective in the topical treatment of various cutaneous hyperpigmentations characterized by hyperactive melanocytes function^[17]^.Arbutin works by inhibiting tyrosinase activity as well as melanosome maturation, and its efficacy is concentration dependent but higher concentrations can lead to a paradoxical hyper pigmentation. a-Arbutin and deoxyarbutin are both synthetic forms with greater tyrosinase inhibition than the original Arbutin.^[18]^[19]Clinical studies have demonstrated that 3% deoxyarbutin is effective in lightening solar lenities in light-skinned patients.^[19]

Botanical extracts:

Extracts mostly contain a combination of two or more classes of compounds that work synergistically to achieve skin lightening. Botanicals connote nature and are hence more acceptable to people. Further, a large number of yet undiscovered plants are available to provide for exotic products and claims for cosmetics. However, it should also be observed that natural extracts may be highly unstable and may not be compatible within formulations. A large number of ingredients have been studied for tyrosinase inhibition and have been processed to make them viable for use in cosmetic products. These are available commercially through suppliers for use as skin-lightening agents.^[10]

Fruits:

Many fruits have skin whitening effect when they are eaten or scrubbed on skin. The leading fruit is papaya, wherein its enzyme papain can whiten the skin. Other notable fruits are lemon, lime, calamondin, and orange; all of these have Vitamin C which is said to have a skin whitening effect.^[5]

Anti-oxidants:

Antioxidants serve to reduce oxidation of tyrosine to DOPA quinone and therefore are shown to have skin-lightening activity. In addition, they act in the melanogenesis pathway, reducing the synthesis of melanin. Exposure to UV radiation results in the generation of free radicals. It has been identiﬁed that ROS (reactive oxygen species) are able to oxidize tyrosinase and DOPA to melanin, and this is one of the major causes for tanning.^[20]Although antioxidants are present represent in tissues, they may not be able to reduce the radicals, depending on the extent of UV exposure.^[10]

Vitamins:

Vitamins have been known to improve skin tone and texture, and they have found remarkable acceptance among consumers. Most of the leading brands of skin-lightening agents that are available commercially utilize vitamins or their derivatives as ingredients. Vitamin A has been used for some decades for the removal of spots in Kingman’s treatment. Further, it accelerates the loss of epidermal melanin by increasing the turnover rate and by promoting the proliferation of keratinocytes.^[10]

Vitamin C also acts as a tyrosinase inhibitor, thereby lightening the skin. Vitamin E provides protection against UV-induced inflammation andhyper pigmentation.^[28]Vitamin E has also been studied in combination therapies with other vitamins as well as in other classes of skin-lightening compounds.^[10]

Niacinamide:

Niacin amide (also known as nicotinamide) are similarly effective as a vitamin because they can be converted into each other within the organism^.^[21]The active form of niacin (vitamin B3), has antioxidant activity interfering with the interaction between and transfer of melanosome from melanocytes to keratinocytes. It has been shown to reduce the total area of hyper pigmentation and increase brightness within four weeks of treatment initiation.^[22]

Peptides:

Peptides are reported to reduce pigmentation through interaction with the protease-activated receptor 2 (PAR-2) of keratinocytes. PAR-2 activation in involved in cell growth, differentiation, and inﬂammatory processes and was shown affect melanin and melanosome ingestion by human keratinocytes [23]. The protease-activated receptor-2 upregulates keratinocytes phagocytosis. The peptide-based antagonist for PAR-2 can be used to regulate melanin ingestion by keratinocytes, thus effecting skin-lightening.Short peptides have also been reported in reducing the enzymatic activity of tyrosinase^.^[24]

Alpha and beta hydroxyl acids:

Alpha and beta hydroxyl acids have been the most important class of compounds that are most widely used in cosmetic preparations. These act as superﬁcial chemical peels that target the stratum corneum to improve skin color and tone.^.[10]They are comparatively pure and inexpensive, and they may be used in higher amounts without many side effects s. A new modified formula (Hetter) is used which contains less phenol and less croton oil.^[24]

Formulation: Cream^[25]:

Types of Cream

1 Emulsion of water and oil

2 Classified as oil in water (o/w) or water in oil (w/o) emulsions

3 O/W creams (e.g. vanishing creams) spread easily and do not leave the skin greasy and sticky

4 W/O creams (e.g. cold cream) are more greasy and more emollient

Criteria of a good quality cream:^[26]

1 Their affectivity should be high.

2 They should give rapid onset of action.

3 They should be biocompatible and bio-miscible.

4 Free from grittiness.

5 They should be smooth.

6 They should be readily washable.

7 They should be non-irritant.

8 They should be non-allergic.

9 They should be non-toxic.

10 They should be physically and chemically stable

Formulation of a cream:^[26]

1 Active ingredient: Drug or raw materials are used as active ingredient.

2 Base: Base is used as carrier of the drug.

3 Preservative: Preservatives are used to protect the drug from microbial content.

4 Antioxidant: It is used to prevent oxidation of the drug that causes degradation.

5 Surfactant: Used to prevent surface tension of two immiscible phases.

6 Complexing agent: It enhances the stability and prolongs action.

7 Viscosity enhancer: Decrease the flow property of creams.

8 Humectants: Protect the drug from moisture.

9 Antimicrobial agents: Among the microbial preservatives used to prevent microbial growth in topical preparations.

10 Emulsifier and bases: Bases that are usually used in the cream preparations are water removable bases. stearyl alcohol, white petrolatum is the usual oleaginous bases. It melts at 38 to 60⁰c which indicates that it melts easily in the body temperature. Na-lauryl sulfate are usually used as emulsifying agents.

11 Complexing agents: EDTA is the mostly used complexing agents that produce complex with active drug to produce more stability and to prolong the duration of action.

12 Antioxidants: Antioxidants used in extended amounts in pharmaceutical industries

Method of preparation:^[27]

Preparation of the oil phase:

Flake/powder ingredients, sometimes dry blended in advance, are dispersed into mineral oil or silicone oil. Heating may be required to melt some ingredients. Hydration of aqueous phase ingredients. Emulsifiers, thickeners and stabilizers are dispersed into water in a separate vessel. Heating may be required to accelerate hydration.

Forming the Emulsion:

The two phases are blended under vigorous agitation to form the emulsion.

Dispersion of the Active Ingredient:

The active ingredient often makes up only a small proportion of the formulation; this must be efficiently dispersed to maximise yield and product effectiveness A method of forming an oil in water cream that involves adding oil to, or adding to oil, a composition which comprises: a) at least one membrane lipid, b) at least one natural amphiphile which is not a primary emulsifier, c) an aqueous phase, and, optionally, d) a hydrophilic medium, so as to form the said oil in water cream.

A preparation in the form of a cream that is based on an oil in water emulsion or dispersion and which includes: a) at least one membrane lipid, and b) at least one natural amphiphile which is not a primary emulsifier, and, optionally, lipid vesicles or liposome.

Evaluation of cream:^[28]

The prepared semisolid preparations can be evaluated for various official and non official specifications.

pH of the formulation:

The pH of formulations was measured by taking formulation in certain amount of water. Then pH of this solution was determined with the help of pH meter (systronics)

Viscosity measurement:

Viscosities of formulations were measured by using Brookfield DV-I (spindle T-D spindle code S94) at specific rotation per minute (rpm). As the rpm increases viscosity decreases. Only in case of gel spindle code S93 was use.

Spredability:

Spredability of the formulation was determined by an apparatus which was suitably modified in the laboratory and used for the study. It consists of a wooden block, which was provided by a pulley at a one end. A rectangular ground glass was fixed on this block. An excess of ointment (about 3 gm) under study was placed on this ground plate. The ointment was then sandwiched between this plate and another glass plate having the dimension of fixed ground plate and provided with the hook. A 1 Kg weight was placed on the top of the plates for 5 minutes to expel air and to provide a uniform film of the ointment between the plates. Excess of the ointment was scrapped off from the edges. The top plate was then subjected to pull of 80 gms. With the help of string attached to the hook and the time (in seconds) required by top plate to cover a distance of 10 cm be noted. A shorter interval indicates better Spredability. Spredability is given in unit gm.cm/sec

Spredability of the formulation may be determined by the following formulation;

S= M x L/T

Where,

L= length moved by glass slide

T= Time in seconds

M=Weight in pan and S= Spredability

Patch Test:

On the first day of skin testing, patch tests are to be performed on the forearms of each volunteer. 5cm x 4cm regions were marked on both the forearms. Basic values for erythema and melanin are to be measured with the help of Mexameter. 1.0g of base and formulation each are applied to the 5cm X 4cm marked regions separately on each forearm. The regions are covered with the surgical dressing after application. After 24 hours, dressings are removed and the measurements of erythema and melanin are repeated on both forearms.

Panel Test:

Every individual is provided with a form prepared previously to test the sensory values of cream. This form consisted of parameters to be evaluated and every parameter is indicating very bad to very good, respectively.Dermatological tests Erythema of the skin are determined on the first day before application of any cream and then on days 7, 14, 21 and 28.

Parameters for Evaluation of Formulation Characteristics.^[29]

Centrifugation test:

Centrifugation test is to be performed for both the base and formulation kept at different storage conditions up toat different time intervals. Phase separation on centrifugation is to be recorded in any of the samples kept at different storage conditions. It is evident that proper homogenization speed during emulsion formulation prevented the base and formulation breakage during stress conditions.

Stability Tests:

Physical analysis, types of cream, pH determination, was analyzed to assure the formulation of desired properties. Stability tests were performed at different conditions for cream to note the effect of these conditions on the storage of creams.Samples are observed with respect to change in color, liquefaction and phase separation.

Phase Separation:

Phase separation wI’ll be observed in any of samples of base and formulation kept at 80 C, 250 C, 400 C and at 400 C + 75% relative humidity up to observation period of 28 days.

CONCLUSION:

Research in the area of skin-lightening agents is an expanding field, with new ingredients being added to the repertoire with every new discovery. Although tyrosinase inhibition is still the most sought after mechanism skin lightening, newer pathways are being identified. It has been noted that ingredients that interfere with the path- ways affecting melanin synthesis and transfer show promise as de-pigmenting agents. Persistent research into skin lightening has also led to new mechanisms being discovered in recent years.

The aspiration for light skin is on an upward curve and can be satisfied only when the cosmetic in the bottle fulfils the promise of fair skin. A careful and complete investigation of the ingredient on the basis of its efficacy and tolerance to individuals through clinical trials is essential to ascertain that the product delivers the promise.

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15. R. Sarkar, P. Arora, and Kv. Garg, “Cosmeceuticals for hyperpigmentation: What is available?,” J. Cutan. Aesthet. Surg., vol. 6, no. 1, p. 4, 2013.

16. S. Dharmana, “Journal of Pigmentary Disorders,” vol. 1, no. 6, pp. 1–4, 2014.

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29. A. H. Alobaidi, E. S. Hamad, K. A. Kudair, and A. M. Alsamarai, “Formulation of Hypopigmentation Cream and Evaluation of its Effect on Skin Pigment. Part I: Formulation of the Product,” Our Dermatology Online, vol. 5, no. 1, pp. 9–13, 2014.

Received on 18.02.2019 Modified on 20.04.2019

Research J. Pharm. and Tech. 2019; 12(10):5059-5066.

DOI: 10.5958/0974-360X.2019.00878.3

Skin Type	Skin Colour	Characteristics
I (Scores 0-7)	White; very fair; red or blond hair; blue eyes; freckles	Always burns but never tans
II (Scores 8-16)	White; fair; red or blond hair; blue, hazel, or green eyes, Fairly skinned Caucasians	Usually burns, tans with difficulty
III (Scores 17-25)	Cream white; fair with any eye or hair colour; very common, Darker Caucasians	Sometimes mild burn, gradually tans
IV (Scores 25-30)	Brown; typical Mediterranean Caucasian skin	Rarely burns, tans with ease
V (Scores over 30	Dark Brown; mid-eastern skin types; Hispanics; Blacks	Very rarely burns, tans very easily
VI (Scores over 30)	Black	Never burns But tan easily

Types	Example
Chemicaltyrosinase inhibitors	Hydroquinone, Kojic acid, Arbutin
Botanicals (essentially from plants,fruits and algae)	Aloe barbadensis leaf extract (Aloesin) Crocus sativus extract Glycyrrhiza glabra, Papaya (Papain), Lemon
Anti-oxidants	PyticAcid, Glutathione, Ubiquinone
Vitamins—A, B, C, E	Niacinaamide (VIT B3), Pantheonic acid (VIT B5), Ascorbic acid (VIT C)
Peptides	Sericin