1.1 History
The history of cosmetics spans at least 6000 years of human history and almost every civilization on earth. The first archaeological evidence of cosmetics custom is found in Ancient Egypt around 4000 BC. The Ancient Greeks and Romans also used cosmetics. The Romans and Ancient Egyptians, not realizing their perilous properties, used cosmetics containing mercury and white lead. Fragrances, particularly 'Frankincense' and 'myrrh' are mentioned in the Bible. The Ancient Egyptians had a huge amount of makeup utensils. One of them is kohl, which was used to outline the eyes. It is made up of lead, copper, burned almonds, soot, and other ingredients. There was a belief that eye makeup could defend against evil spirits and develop the eye sight. Even the poor wore eye make-up in ancient Egypt. The production of cosmetics during ancient Rome was usually done by female slaves called Cosmetae. From the Middle East cosmetics were used in Persia. After Arab tribes converted to Islam and conquered those areas, in some areas cosmetics were only restricted if they were to disguise the authentic look in order to give the wrong impression about or cause unrestrained desire. In Islamic law, there is no prohibition on wearing cosmetics, but there are certain requirements that the cosmetics must not be made of harmful substances. The Chinese people began to stain their fingernails with gum Arabic, gelatin, beeswax and egg from around 3000 BC. The colors used represented social class i.e. Chou dynasty royals adorned gold and silver, later royals wore black or red. The lower classes were forbidden to wear bright colors on their nails. In Japan, the geishas wore lipstick made of crushed safflower petals to paint the eyebrows and edges of the eyes as well as the lips, and sticks of bintsuke wax while a better version of the sumo wrestlers' hair wax were used by them as a makeup base. Rice powder colors were used for the face and back and Rouge for contouring the eye socket and defining the nose. The geisha would also sometimes use bird droppings to assemble a lighter colour.

1.2 Definitions:-
Common Definition : Cosmetics are rigorously defined as the agents with the power to adorn, embellish or beautify, affected superficially only. They are the substances or preparations which are applied for cleansing, beautifying, promoting pleasant appearance or altering it without affecting the functions of the body.
Asian Definition : Any substance or preparation intended to be placed in contact with the external parts of the human body or the mucous membranes of the oral cavity or the teeth with a purpose exclusively for cleansing, perfuming, changing their substantial appearance, correcting the body odors and/or protecting or keeping them in good and well maintained condition.
Canada Definition : 'Cosmetic' includes any substance or mixture of substances manufactured, sold or represented for use in cleansing, improving or altering the complexion, skin, hair or teeth including deodorants and perfumes.
EU Definition : A 'cosmetic product' shall mean any substance or preparation intended to be placed in contact with the different external parts of the human body i.e. epidermis, hair system, nails, lips and external genital organs or with the teeth and the mucous membranes of the oral cavity with a view exclusively to clean, perfume, change their appearance and correct the body odors while protecting them in good provision.

Japan Definition : The term 'cosmetic' means any article intended to be used by means of rubbing, sprinkling or by parallel application to the human body for cleaning, beautifying, promoting attractiveness, altering the appearance of the human body, and for keeping the skin and hair healthy, provided that the action of the article on the human body is gentle.
USA Definition : The idiom "cosmetic" means subjects intended to be rubbed, poured, sprinkled, sprayed, introduced into or otherwise applied to the human body or any part thereby cleansing, beautifying, promoting attractiveness or altering the appearance (OR) articles intended for use as any of the components not containing soap.
1.3 Introduction to cosmetics
Cosmetics are rigorously defined as the agents with the power to adorn, embellish or beautify, affected superficially only and are intended to improve the physical appearance of the people. They are the substances or preparations which are placed in contact with the external body surface and thereby applied for cleansing, beautifying, promoting attractiveness or altering the physical appearance without affecting the functions of the body.
Cosmetics are not Over the Counter (OTC) drugs or prescription drugs. They are used merely to improve the appearance and are available at all the retail and non-retail stores other than pharmacy outlets. Cosmetic products have no purpose without the human skin hence their value, efficacy, virtue and problems are valid only within the framework of human skin. Cosmetics are one of the highly utilized necessities of women. These include: skin care products and makeup products. There are many brands and types of cosmetics in market. Some females buy cosmetics because of the brand name while some buy it through recommendations.
On the competitive market, nowadays a good packaging design is the key component of successful sales. In order to attract the consumers to purchase the product, packaging should be done in a beautified manner. Packaging design creates an image of the brand and creates a significant impression on the consumers. Creative packaging catches the attention of the products to be launched.
There are number of new products being launched in the pharma market. Products ranging from skin care, hair care and various beautifying products are being revised time to time. Moreover products that use natural ingredients and are free of synthetics, parabens and other toxic chemicals are of high sales. They should be cruelty-free with a fair trade. The company should try to reduce packaging and use eco-friendly manufacturing processes.

1.4 Criticism and Controversies
The popularity of cosmetics increased rapidly during the 20th century. They are widely used by girls at a young age, especially in the United States. Due to the rapid usage of make-up, many companies, from high-street brands like Urban Decay to higher-end products like Estee Lauder, supply to this expanding market by introducing new flavored lipsticks, glosses and face powders, cosmetics packaged in glittery, sparkly packets. The marketing and advertisement of these products are increasingly done using younger models. The social consequences of younger ambassadors and the cosmetic brands caught much attention in the media over the last couple of years. Criticism of cosmetics has generated from an extensive variety of sources including some writers and public interest groups. Criticism of cosmetics has come from a variety of sources including some feminists, Islamists, Christians, animal rights activists, authors and public interest groups. There is a growing awareness and preference for cosmetics that are without any supposedly toxic ingredients especially those derived from petroleum, sodium lauryl sulfate (SLS), and parabens. SLS causes dermatitis and parabens causes skin irritation and allergies. Prolonged use of makeup has also been associated with thinning of the eyelashes. Various studies from the patch testing concluded that the synthetic fragrances which are made of certain ingredients, causes allergy.

2. Introduction to skin
The skin is a complex multipurpose organ with huge amount of scientific study. It is the largest part of human body acting as a protective cover for the internal body organs and tissues. It performs various physiological functions of the body. Skin has the capability to bear all the external wear and tear phenomenon with a wide range of products which are painted, splashed, sprayed or massaged on the skin surface. There is a constant intricacy of the chemical substances present in the skin, their interactions with the body and skin physiology.

Figure 1: Basic anatomy of the skin structure including cells, layers, glands and blood vessels

The integument is the largest organ of the body, making up 16% of body weight having a surface area of 1.8 meter square. It performs important functions like forming a physical barrier to the environment, allowing and limiting the inward and outward route of water, electrolytes and various substances thus providing protection against micro-organisms, ultraviolet radiation, toxic agents and mechanical abuse.
2.1 Structure and Functions of skin
The skin and its derivatives forms the integumentary system. The skin is an external organ which covers largest part of the body, constituting 15-20% of its total mass. The basic functions of skin include:
' Act as a barrier which prevents fluid loss, protects against toxic and infections agents, radiation etc
' Temperature control
' Acts as the peripheral outpost of the immune system
' Also involved in an organ of sexual attraction
' Provides a protective barrier against mechanical, thermal and physical injury and noxious agents.
' Prevents loss of moisture.
' Reduces the harmful effects of UV radiation.
' Acts as a sensory organ.
' Plays a role in immunological surveillance.
' Synthesis of vitamin D3 (cholecalciferol).
' Has cosmetic and social associations

2.2 Main Functions
Functions of the skin can be easily remembered by the acronym 'SHAPES' as given below:
' S ' Sensation - response to heat, cold, pressure, and pain
' H ' Heat regulation - maintains body temperature of 98.6
' A ' Absorption - substance can enter the body through the skin and affect it to minor degree
' P ' Protection - from bacterial invasion
' E ' Excretion - sweat glands excrete perspiration
' S ' Secretion - sebum is secreted by the sebaceous glands
To have knowledge of the structure of skin from a broader aspect, one may segregate it into three layers. Epidermis forms the stratified squamous epithelium consisting of mainly keratinocytes. Dermis forms the structural foundation of the skin and supports its superficial and deep layers. Sub dermis forms the deep subcutaneous adipose layer and acts as a fat as well as heat storage.

Figure 2: Various layers of the skin
2.3 Epidermis
It is the layer of keratinocytes with stratified epithelium and is derived from ectoderm. Keratinocytes act as skin stem cells and are located on the basal lamina forming 95% of the epidermal cells while the 5% forms Melanocytes, Langerhans cells and Merkel cells. They divide, migrate upwards acquiring a large amount of cytoplasm and many desmosomes in this layer. The epidermis grows continuously and undergoes desquamation process thereby maintaining its required thickness. Epidermis is further divided into four distinct layers on the basis of different cells present. Stratum lucidum is the fifth layer of epidermis which is seen occasionally.
The uppermost layer is stratum corneum composed of keratin cells called corneocytes. The outermost layer is the major layer responsible for the barrier function of skin. Epidermis is entirely dedicated to its production. It is composed of 15-20 layers of flattened, non-nucleated keratinized cells; filled with filaments of keratin. The surface cells of the stratum corneum are continuously desquamated i.e. skin flaking. The cornified envelope surrounding each corenocyte includes involucin, loricrin, keratolinin, pancornulins and cornifin. The cells of this layer are highly differentiated. They lose their cytoplasmic organelles and nucleus thus filling itself entirely with keratin filaments. The plasma membrane of the cornified keratinized cells is coated from the outside, in the deeper portion of this layer, with an extra cellular layer of lipids forming major constituent of the barrier of epidermis. The thickness of the skin varies from 1mm to 5mm.
The next layer which is immediately attached below is the stratum lucidum. Observed only in the thick parts of the skin, this layer has a refractile appearance when viewed under a microscope. The process of keratinization is advanced in this layer containing eosinophilic cells.
Stratum granulosum is the layer after stratum lucidum containing numerous stained granules. Here, the cells become flat and accumulate dense, basophilic granules in the cytoplasm called the keratohyalin granules. These granules contain cystine-rich and histadine-rich proteins which are precursors of filaggrin, a protein which when activated, promotes the aggregation of filaments of keratin. By the influence of filaggrin, the keratin filaments align into the disulphide cross-linked macrofibres. At the same time, the nucleus and the cytoplasmic organelles disappear, and the keratinocyte is reduced to a flat squame of keratin called the corneocyte.
The layer after stratum granulosum is stratum spinosum having many cells which makes it a thick layer. In this layer, the cells enlarge and acquire numerous desmosomal connection plaques that will stabilize the network of cells. Prickle cells are rich in ton filaments that are constituted by intermediate filaments of keratin that attach themselves to the desmosomes. Diseases that affect the desmosomes can lead to breaks in the fabric of the keratinocytes with formation of vesicles. In pemphigus, auto-antibodies are directed against desmosomal proteins, leading to their destruction with lack of cellular adhesion. The cells are large and exhibit numerous cytoplasmic processes or spines.
The fourth layer of epidermis is the stratum basale. It is a continuous layer which is 1-3 layers of cuboidal cells (~12??m in diameter) which have large nuclei with dense cytoplasm as well as the true resident skin cells. A large variety of different cell types migrate through the different layers of the skin. The components of the skin are intimately linked with this migration, and the 'cross-talk' between the layers. This shows that the skin is a dynamic organ
2.3.1 Functions of the epidermis:
' Serve as a barrier to harmful exogenous substances, chemicals and pathogens
' Fundamental as a retainer of tissue proteins and fluids

2.3.2 Diseases of the epidermis:
Characteristics Scabies Pediculosis capitis Pediculosis corporis Pediculosis pubis Tungiasis HrCLM
Infective agent Sarcopes scabiei Pediculus humanus var. capitis Pediculus humanus var. corporis Phthirus pubis Tunga penetrans A. caninum, A. braziliense
Taxonomical classification Acaride (mite) Phtiraptea (louse) Phtiraptea (louse) Phtiraptea (louse) Siphonatera (flea) Helminths(nematode)
Life-cycle on-host on-host on-host on-host Partially on host Partially on host
Occurrence Worldwide Worldwide Restricted to cold regions Worldwide Caribbean, sub Sahara Africa, South America Hot climate countries predominently
Seasonal variation Peak during cold seasons Peak during cold seasons Inconsistent data Peak during cold seasons Peak in hot and dry seasons Peak in rainy seasons
Animal reservoir none none none none Dogs, cats, pigs, rats Dogs, cats

Table 1: Diseases of the epidermis layer of skin
2.4 Dermis:
The dermis varies in thickness, ranging from 0.6 mm on the eyelids to 3 mm on the back, palms and soles. It is found below the epidermis and is composed of a tough, supportive cell matrix. Two layers comprise the dermis:
' Thin papillary layer
' Thicker reticular layer.
The papillary dermis lies below and connects with the epidermis. It contains thin loosely arranged collagen fibres. Thicker bundles of collagen run parallel to the skin surface in the deeper reticular layer, which extends from the base of the papillary layer to the subcutis tissue. The dermis is made up of fibroblasts, which produce collagen, elastin and structural proteoglycans, together with immunocompetent mast cells and macrophages. Collagen ??bres make up 70% of the dermis, giving it strength and toughness. Elastin maintains normal elasticity and flexibility while proteoglycans provide viscosity and hydration. Embedded within the firous tissue of the dermis are the dermal vasculature, lymphatics, nervous cells and fibres, sweat glands, hair roots and small quantities of striated muscle.
The dermis is the structural 'foundation' to the epidermis, bound externally by the junction with the epidermis and internally by subcutaneous fat. It contributes 15-20% of total human body weight. It varies in thickness, thick in the back + thighs to thin on the eyelids. Consists of cellular elements (fibroblasts, mast cells, histiocytes, Langerhans cells, lymphocytes, eosinophils) with a supporting matrix/ground substance embedded with protein fibres (collagen, elastic fibres +microfibrillar components). There are also embedded nerves, blood vessels, lymph vessel, muscles, apocrine units + eccrine units.
The dermis arises from the mesoderm, which is brought into contact with the inner surface if the epidermis during gastrulation. The mesoderm not only provides a dermis, but is also essential for inducing differentiation of epidermal structures e.g. the hair follicle. The embryonic dermis is at first very cellular, and the interface with the epidermis is very flat. By 12 weeks, the interface is undulated (known as the rete-ridge pattern) + fibrillar components are evident. By 24 weeks, dermal papillae develop
The dermis is divided into The superficial thin papillary dermis= ADVENTITIAL DERMIS' this interdigitates with the ridged underside of the epidermis. Histologically appear pale; consists of abundant ground substance with a highly developed microcirculation but thin irregular collagen fibres, delicate elastic fibres + numerous fibroblasts. The larger underlying reticular dermis = RETICULAR DERMIS ' this blends with the subcutaneous fat. Makes up the bulk of the dermis ' consists of irregular course elastic fibres, thick regular collagen bundles, fewer fibroblasts, microcirculation + ground substance. In specialised regions, e.g. the nipples, penis, scrotum + perineum ' there are also smooth muscle fibres within the reticular dermis.

2.4.1 Functions of Dermis
' It gives strength and toughness.
' Elastin maintains normal elasticity and flexibility
' Proteoglycans provide viscosity and hydration

2.4.2 Diseases of the Dermis
Name of Diseases Synonyms Outline Clinical Features Pathogenesis Treatment
Striae Striae distensae, Striae atrophicae Slightly concave, linear cutaneous atrophy, thighs and lower abdomen commonly affected, stretching especially in pregnancy and adolescence. Several millimeters wide and 10 cm long. They run roughly parallel each other. The color is rose pink in the early stages, becoming grayish white later on. Gluco- corticoid inhibits collagen production, reduction of connective tissue, wound healing is impaired, resulting in Striae and atrophy in the skin Subsides with age, nonetheless, irreversible and does not disappear completely.
Solar elastosis Actinic elastosis, Senile skin atrophy Dermal degeneration caused by excessive exposure to sunlight, this is an aging change and atrophy of the skin. Skin becomes thin and yellowish, degeneration of dermal elastic fibers, skin slackens, Large folds of skin form on the face, neck and joints. Reduction of collagen fibers, the sweat glands and oil glands decrease in size and number, and subcutaneous fat tissue decreases. -
Lichen Sclerosus et Atrophies LSA Chronic disorder with a preference for the 'anogenital' lesion on the trunk of middle-aged and elderly women. White, flat-topped papules of 2 to 3 mm in diameter aggregates, firm white plaques, shrinks and form crepe-like appearance, inflammation, itching and pain. Hereditary factors, endocrine abnormality, immune mechanisms involved, Auto antibodies against extracellular matrix ECM1 found in the patient's serum. Topical steroids and Tacrolimus ointment can be applied.
Wener's syndrome Adult progeria Premature aging, occurs in systemic tissue at adolescence, mutation in RecQ DNA helicase gene, RECQL2, autosomal recessively inherited. Subcutaneous fat and muscle having atrophy adhere to the subcutaneous layer, Scleroderma-like articular contracture and atrophic hardening of the skin, the nose becomes thin and pointy due to atrophy, Keratinization and ulceration on the soles, pigmentation on the whole body, telangiectasia, and subcutaneous calcinosis occurs, Gray hair and alopecia. mutation in RECQL2 encoding the DNA helicase on chromosome number 8. Most patients are short-lived due to myocardial infarction
Rothmund-Thomson syndrome Reticular erythema on the cheek Autosomal recessive, the cause is genetic mutation. In infancy and childhood, skin atrophies and reticular or diffuse erythema occurs on the face, juvenile cataract appears. One of the causative genes is RECQL4 encoding the DNA helicase, on chromosome number 8. -
Table 2: Diseases of the dermis layer of skin
2.5 Nerves of the Skin
There are three kinds of nerves which performs various functions related to the skin. Sensory nerves fibres are receptors and send messages to the brain which causes reactions to heat, cold, touch, pressure, and pain. Motor nerve fibers which are attached to the hair follicles, are dispersed to the 'arrector pilli' muscles which may cause goose bumps when sensations like fright or cold are experienced. The Secretory nerve fibers help in the regulation of the excretion of perspiration from the sweat glands and regulate the flow of sebum to the surface of the skin.
2.6 Glands of the Skin
There are two types of duct glands enclosed in the skin which draws out minerals from the blood to generate new substances. The Suderiferous glands are the sweat glands and the Sebaceous glands are the oil glands. Sweat glands excrete perspiration. This secretion is odorless when excreted, but in a short period of time produces an unpleasant odour due to the bacteria on the skin's surface that feeds on the fats of its secretion. Perspiration is controlled by the nervous system. Daily about 1-2 pints of liquid containing salts are excreted through the sweat pores of the skin. The sweat glands consist of a coiled base or fundus and a tube-like duct that ends at the skin surface forming the pores. They are numerous on the palms, soles, forehead and armpits. Body temperature is regulated by the sweat glands that also support in the elimination of waste.
Oil glands secrete sebum through little sacs whose ducts open into the hair follicles. These glands are present in all parts of the body except the palms and soles. The oily substance produced by the oil glands is called sebum. Sebum lubricates the skin and conserves the pliability of the hair. When the duct becomes clogged with hardened sebum, a blackhead is formed.

3. What are Skin Cosmetics?
Face and body decoration is among the oldest and most prevalent of human behaviors. Over 75,000 years ago, paint pigments have been found in archeological contexts which prove that people may have adorned themselves with body smears before they covered their bodies with clothing. The performance of painting has continued since then and people in all societies decorate their faces and bodies. Robert Brain, a famous entity penned in his cross-cultural explanation of the decoration of the human body that 'Body decoration in some societies is renowned arts while some may term them as a fine art. However for myself as an anthropologist, the most interesting fact which has popped out is that the transformation of the human body through fine art is a basic need which is universally practiced by all the humans of the world, even the most fashionable or the most simple.' Fundamental skincare has been described as a multiple-step routine, involving four essential steps:
1) Cleanse
2) Treat
3) Moisturize
4) Protect
Cosmetics are one of the highly utilized necessities of women. These include:
' skin care
' makeup products
3.1 Skin care
Skin is bombarded with dirt and dust particles and if the makeup is applied for longer duration then grease is bound to be added to the list. Most make ups are very oily and cannot be removed with water alone. Soaps like deodorant soaps, medicated soaps or soap-less soaps, washing creams or lotions, and cleansers that come in cream or lotion form can be used for effective cleansing of the skin. Toners, astringents and clarifying lotions are also available at higher cost and of better quality. Hence dirt is removed and washed away by these soaps due to the chemicals like surfactants and emulsifiers present in them. Molecules attaching to both water and grease are present in these surfactants which dissolve the grease and oils from human skin. A non soap cleanser is usually preferred ideally for the significant cleansing of skin. Preservation of the skin's natural lipids keeps the skin's own moisture locked in. The key principles for a clean and healthy skin while using cosmetics are:
' Excess washing leads to dry skin.
' Excess usage of soap leads to dry skin.
In order to change the biology of the skin, pharmaceuticals and even certain cosmeceuticals are used. While medicated creams do require FDA approval, the cosmeceuticals don't require them. The important properties to watch for in any cosmetic product are irritation, acne and allergic reactions. Sensitivities ranging from red, rough and stinging rash to pimple outbreaks are enough to switch products immediately.

3.2 Make up products

Products Description
Primer Reduces the appearance of pore size, prolongs the hold of makeup, and allows for a smoother appliance of makeup and are used before foundation.
Concealer Mainly used to cover up any imperfections of the skin. It is often used for any extra coverage needed to cover blemishes, under eye circles and provides more meticulous coverage with contouring the face like nose, cheekbones, and jaw line.
Foundation Used to smooth out the face and cover spots or patchy skin coloration. Usually a liquid, cream or soft mousse is available.
Face powder Used to set the foundation, giving it a matte finish, conceals small flaws or blemishes. Tinted face powders may also be worn as a light foundation.
Rouge / blusher Used to bring out the color in the cheeks and appearance of a more defined cheek bone. Rouge comes in powder, cream and liquid forms.
Bronzer Used to give skin little color by adding a golden or bronze glow thereby used for contouring. It is available in either matte, semi matte/satin, or shimmer finishes.
Eye products Enhance and elongate the size of the eye, used to darken, lengthen, thicken, or draw attention to the eyelashes, also defines the brows.

Table 3: List of makeup products used in the cosmetic industry

3.3 Fundamental types of ingredients used in Cosmetics
3.3.1 Organic and natural ingredients
In the competitive market, handmade and certified organic products are becoming more main stream. Health concerns endure regarding the presence of harmful chemicals in the cosmetic products. Apart from color additives, cosmetic products and their ingredients are not a substance to regulation before their release in the market. Many cosmetic companies claim to produce 'all natural' products and these claimed to be organic, should be certified by the USDA.
3.3.2 Synthetic Ingredients
The main ingredients in mineral make up are usually coverage pigments such as zinc oxide and titanium dioxide which are also physical sunscreens. Other ingredients include mica and pigmenting minerals such as iron oxide, tin oxide and magnesium myristate. These usually do not contain synthetic fragrances, preservatives, parabens, mineral oil, and chemical dyes. For this reason many dermatologists believe mineral makeup to be pure to the skin. However, some makeup contains bismuth oxychloride, which irritates the skin of sensitive individuals. Others also contain talc over which there is some controversy because of its tendency to clog pores and thus causes acne.

3.4 Delivery of Cosmetic ingredients to the skin
The era of cosmeceuticals is prevalent which comprises of cosmetics companies making cosmetics while the Pharmaceutical companies making medicines. Cosmeceuticals are skincare products that combine cosmetics and medicines. In order to deliver necessary ingredients inside skin cells, the barrier function of the skin must be defeated selectively without any alteration. The outer layer of the skin, the stratum corneum, has layers of keratin and is considered to be particularly difficult to penetrate.
There are major entry sites into the skin i.e. pores, hair follicles and spaces between cells that containing an oil and water fluid matrix. An effective cosmetic is designed with the objective to improve the mechanism of the cells, yet not destructing the overall skin reliability. It requires considerable biochemical skill with the expertise in mixing an orchestration of ingredients. Vitamin E, however penetrates the layer of stratum corneum to a deep extent inorder to serve as a potent antioxidant thereby fighting skin aging and sun damage. However, Vitamin E Acetate has proved to be a better antioxidant. In general, esthers of substances like Potassium cetyl phosphate are more easily transported across the skin surface. Vitamin A palmitate is the ester of Vitamin A and palmitic acid, having better skin penetration to its target site.

3.5 Classification of Cosmetic Products

3.5.1 Category I products:
Before the manufacturing, import, sale or supply of the Category I cosmetic products, they should be licensed:
' Cosmetic products including eye creams, eye shadows, eyeliners and mascaras
' Cosmetic products for application on the lips including lipsticks, lip colors and lip creams
' Oral or dental hygiene products including mouth refreshers and dentifrices
' Hair dyes
3.5.2 Category II products:
All other cosmetic products are classified as Category II cosmetic products which do not require licences for importation, sale or supply. They include:
' Skin lotions including pre-shave, after-shave, eau-de-cologne and hand lotions
' Creams and lotions including after-shave, cold cream and vanishing cream
' Cosmetic oils and moisturizers
' Foundations and anti acne agents
' Cheek colours
' Eyebrow colours
' Sunscreen, suntan and sunburn prevention preparations
' Skin whitening agents
' Talcum, face, creamy, pressed, loose, paste, baby and body powders
' Depilatories
' Face packs and face masks
' Bath oils, bath salts and other bath preparations
3.6 Skin Whitening agents
Skin whitening products are commercially available for cosmetic purposes in order to obtain a lighter skin appearance. They are also used in treating disorders such as melasma or postinflammatory hyperpigmentation. They are known as viable inhibitors of tyrosinase, the key enzyme in melanogenesis. The maturation of this enzyme or the transport of pigment granules (melanosomes) from melanocytes to surrounding keratinocytes is inhibited. Melanocytes are situated on the basal layer of skin and are enclosed by approximately 36 keratinocytes. Transportation of the melanin via dendrites to the overlaying keratinocytes is done.
The melanin pigment is a polymer produced inside the melanosomes and is synthesised from the amino acid L-tyrosine that is converted by the enzyme tyrosinase to dopaquinone. This reaction continues spontaneously via dopachrome to the monomeric indolic precursors of the black-brown pigment 'eumelanin'. However, some other enzymes, like the tyrosinase related proteins (TRP-1) and dopachrome tautomerase (TRP-2) plays a vital role in melanogenesis in vivo. When reacted with cysteine, dopaquinone forms 2- or 5-S-cysteinyldopa that generates the benzothiazine precursors of the red/yellow 'pheomelanin' polymer. In general, a mixture of pheomelanin and eumelanin polymer is produced and deposited onto the melanosomal matrix proteins.
Since there is a variety colours in skin and hair of people throughout the world, one may expect that the composition of the mixed melanins is regulated.

3.7 Skin Anti aging agents
Natural ingredients in the form of phytonutrients, microbial metabolites, dairy derived actives, mineral nutrients and animal protein components have long been believed to benefit healthy skin ageing. Recent scientific evidence has served to strengthen this concept and validate the efficacy of several natural actives at the molecular level in keratinous tissues.

3.8 Skin Thickening agents
Raw materials for natural cosmetics consist of natural polysaccharides which, when mixed and beaten together with water or hydrolates, produce protecting gels and soften the skin. Examples of these agents are Aloe Vera Gel, Circulation Gel and Tea Tree Gel. These thickening agents can also be used as secondary emulsifiers in creams and lotions. The main task of a thickener for surfactant formulations is to increase the viscosity however, the consumer insight is also important. The flow characteristics and the application properties have been considered. Good stabilizing effects can be obtained by choosing by the right rheological profile and a low temperature dependence of the final viscosity. In order to save costs, the efficiency of the thickeners is very important. Conditioning, moisturizing, refatting and solubilizing have to be always considered when choosing a thickener system.

3.9 Skin Moisturizing agents
Moisturization inhibits trans epidermal water loss by occlusion. Water originates in the deeper epidermal layers and moves upward to hydrate cells, eventually being lost to evaporation. Research suggests that the stratum corneum acts an active membrane consisting of intercellular lipids (i.e. ceramides, cholesterol and fatty acids), thereby forming a water-barrier function. Moreover, the stratum corneum contains a natural mixture of amino acids, lactates, urea and electrolytes which helps in retaining the water. Dry skin is experienced by a loss of continuity of the stratum corneum along with the moisture content being less than 10%.

3.10 Skin Anti Acne agents
Acne vulgaris is one of the most common conditions for which all patients including patients with derma care. The multi factorial pathogenesis of acne appears to be the same in Caucasians. However, there is controversy over whether certain skin biology characteristics. Azelaic acid and dicarboxylic acid is produced from the organism responsible for Pityriasis versicolor and is useful in the treatment of acne. Formulated in a 20% cream, azelaic acid is often used alongside with other topical agents such as antibiotics or retinoids for greater efficacy. Azelaic acid has a property of low irritation and its ability to inhibit tyrosinase, an enzyme necessary for the production of melanin. Generally, topical antimicrobials are used in combination therapy for milder cases of acne.

3.11 Role of Food and Drug Administration (FDA) in Cosmetic Industry
The approval of the FDA is not needed while selling any cosmetic product. FDA does not review cosmetics or their ingredients, before they are sold to the public. But FDA urges cosmetic makers to perform whatever tests are needed to prove whether their products are safe and secure. Cosmetics makers must put a warning statement on the front labels of products that have not been tested for the safety measures which reads, "WARNING: The safety of this product has not been determined."
FDA requires safety testing for color additives used in cosmetics. Cosmetics should only contain approved and certified colors. Three kinds of labels are listed on the cosmetic products.
' FD&C - foods, drugs and cosmetics
' D&C - drugs and cosmetics
' External D&C - drugs applied to the surface of the skin and cosmetics

Figure 3: Myth and Fact of drugs in Cosmetics
A cosmetic manufacturer also does not have to report product injuries. FDA collects this information on a voluntary basis only. Cosmetic manufacturers send the reports to the FDA who wants to be a part of this program. Product recalls are also taken as the voluntary actions. FDA does not keep a check on the cosmetic recalls rather it monitors cosmetic manufacturers that do a recall. FDA must first prove in the court that a cosmetic product is a threat and prove it to the law before it can be taken off the market.
Various safe herbal drugs which can be used in cosmetic Preparations
Organic aloe vera potent healer, regenerative agent especially for burns, rashes or sunburn, aids digestion, soothes stomach ulcers and improves regularity of the colon
Purified water Removes chemical through osmosis, which stunts the chemicals sideways thus leaves the remaining water chemical free.
Organic Rosehip Seed Oil Cell regeneration, collagen and elastin production, firm smoother and more elastic skin, essential fatty acids (Vit E) help achieve healthy skin
Organic Avocado Oil (Persea Gratissima) Ideal for mature skin and penetrates deep into the skin, reduces wrinkles and fine lines, protects from UV rays, pollution and free radicals, acts as natural alcohol creating it anti-bacterial, rich in vitamins A and D
Organic Jojoba Oil (Simmondsia Chinensis) Used as a carrier for jojoba oil which is rich in vitamins E, B and minerals like copper, zinc and silicon chromium, antimicrobial properties, nourish and revitalize the skin.
Organic Sweet Almond Oil (Prunus Amygdalus Dulcis) Rich in vitamin D, glucosides, minerals, oleic and fatty acids, helps in conditioning the skin for younger and softer looking skin, gives relief during itchy, dry and inflamed skin experienced during pregnancy
Organic Tangerine Oil (Citrus Nobilis) Calms the senses, relieves fatigue, stress, refreshes, preservation of fluid, prevents stretch marks
Organic Shea Butter (Butyrospermum Parkii) Exceptional skin protector, treats scars, stretch marks, eczema, burns, blemishes, severely dry skin
Non-GMO Lecithin (soybean oil) Fine restoring agent, soften and hydrates the skin, effective, capable of penetrating deep in the skin, delivery to the cellular level
Organic Unrefined Beeswax (Cera Alba) Hydrates, increases moisture and protects the skin
Organic Neroli (Citrus Aurantuim Amara) Intense aroma, benefits the delicate, adult and dry skin.
Organic Lavender (Lavendula Angustifolia) Improves circulation, reduces cellulite, water retention, acne prone skin, antiseptic Regenerates, calms and heals all skin types.
Olive Extract Effective antibacterial and anti-fungal agent which heals and soothes
Vitamin E Elevated essential fats and antioxidants wears away dead skin cells and replaces with healthy new cells, moisturizes
Natural Gum Available from tropical trees and plants, thickener, emollient, binder

Table 4: List of some safe and stable drugs used in cosmetic preparations

Various toxic drugs which should be avoided in cosmetic preparations
Dimethicone and Cyclomethicone (silica) Used as emollients, give silky and smooth texture. However, clogged pores, blackheads, irritation to the eyes and skin
Mineral Oils (Paraffin oil and wax, liquid Paraffinum, Petrolatum) Moisture sealer, seals the skin like a plastic coating, clogs pores, prevention of elimination of toxins thus acne
Butylene Glycol and Proplylene glycol Rancid oils forms free radicals and damage the skin by penetration, protein and cellular structure will weaken, highly toxic
Cocoamidopropyl Hydroxysultaine Multipurpose drug, foaming, conditioning, thickener, but causes stinging, redness and skin burns if sensitive, penetrates deep into the skin so more harmful
Triethanolamine Balances pH in cosmetic preparations, cuases irritation, corrosive to the eyes, harms the immune and respiratory systems
Volatile Alcohols Cleanses and disinfect, but they irritate, dehydrates and shred the skin to its natural barrier
Phenoxy ethanol Used in cosmetics to kill bacteria and keep the formula stabilized but is toxic to the kidneys and bladder, harms reproductive system, damages the eyes. In a number of animal studies its toxicity was noticeable when used in moderate doses, breakdown to the brain and nervous system
Methyl Paraben Cheaper, rapidly absorbed into the skin, cause for eye and skin irritation, allergies affects the respiratory tract, most evil when combined with benzoic acid thus very toxic, traces of the parabens have been found in breast cancer cells
Talc Increases in the commencement of ovarian cancer when there has been regular use to the genital area
FD & C yellow no.6 Gives only color, but causes allergic reactions and can activate asthma, carcinogenic and expelled in some countries.
Fragrance Allergic reactions, headaches, dizziness, skin irritation, aggressive coughing

Table 5: List of some toxic drugs used in cosmetic preparations

4. Active Pharmaceutical Ingredients in Cosmetics
4.1 Skin Whitening agents
Skin-lightening agents are those that cause depigmenting activity on human skin, and
they have been widely used in dermatology and cosmetics. A huge number of actives
both from biological sources and synthetic chemical compounds have been reported in
the prose. Their mechanism of action is generally through:
(a) Tyrosinase inhibition
(b) MITF inhibition
(c) Down regulation of MC1R activity
(d) Interference with melanosome maturation and transfer
(e) Melanocyte loss, exfoliation

Figure 4: Effect of UV on melanocyte synthesis

In cosmetic formulations hydroquinone (HQ) has been widely used as an successful whitening agent but it has been forbidden recently due to serious safety concerns. Its use has been connected with mutagenicity and the increased occurrence of ochronosis in African countries. Other compounds often used are kojic acid, arbutin and azelaic acid. Arbutin is a glycosylated form of HQ that is present in the bearberry extracts and is synthesized from HQ by glucosidation. A new derivative, deoxyarbutin was prepared by elimination of all hydroxyl groups from the glucose side chain of arbutin which showed much lower cytotoxicity than arbutin. In the large variety of whitening products, nowadays the use of different natural whitening agents is noticeable and is commercially available. The utilization of kojic acid and arbutin is still common because these agents have repeatedly been demonstrated to be effective whitening agents. In Meladerm and Lucederm preparations, the use of bearberry extracts (a natural source of ??-arbutin) strengthens the effect of ??-arbutin. Among the natural extracts, 'mulberry' and 'licorice' are popular components added to the skin whiteners. The isolation of their active components and their effect on tyrosinase inhibition (TI) and pigment reduction (PI) has been described. Also lemon extract is used in the preparations like Skin Bright, Lucederm and Meladerm as a potent skin bleaching ingredient. However, it can only be used at low concentrations because it easily causes skin irritation. Sophora species from which several active compounds have been isolated, act as potent inhibitors of tyrosinase and pigment production. In this case it is combined with Kiwi fruit (Actinidia Chinensis) which contains flavonoids e.g., quercetin that may be responsible for tyrosinase inhibition. Niacinamide, interferes in melanosome transfer to keratinocytes and used in the formulations of Meladerm and Lucederm. One of the components of the Meladerm preparation is TegoCosmo which contains a guanidine compound that acts on tyrosinase activity. Another component is Gigawhite that contains various plant extracts from the Alps being tested on 10 subjects of Asian origin. Its bleaching effects may partly be attributed to tyrosinase inhibition. The dilemma arises whether the increasing amounts of potentially active whitening ingredients will cause additive effects or will reduce the effects of the most potent ingredients by competitive inhibition. Some companies still utilizes single synthetic compounds. For instance Lipotec uses dimetylmethoxy chromanyl palmitate in its product 'Chromabright'. This showed lightening activity in a group of 20 Asian volunteers after 30 and 60 days. It performs a new mechanism of action targeting the peroxisome proliferator- activated receptor (PPAR). Their active ingredient named O.D.A. thus reducing tyrosinase mRNA expression. Thus, approaches for skin whitening have broadened in the recent years. The utilization of single agents inhibiting tyrosinase is in many cases extended to the use of complex mixtures that target different mechanism like tyrosinase expression, transfer of melanosomes, antioxidant and anti-inflammatory effect.

4.2 Classification of Skin Lightening ingredients

4.2.1. Chemical tyrosinase inhibitors
Some of the well known tyrosinase inhibitors are hydroquinone, kojic acid, and similar types of compounds.

Hydroquinone is considered to be the gold standard for depigmenting agents. It interacts with copper at the active site of the enzyme tyrosinase, resulting into a decrease in its activity by nearly 90%. It not only limits tyrosinase but also oxidizes membrane lipids and proteins through generation of reactive oxygen species. The radicals generated inhibits cellular metabolism by affecting DNA and RNA synthesis. It is generally administered at concentrations ranging from 1.5% to 5% concentration. The use of hydroquinone in cosmetics has reduced because of the various adverse side effects due to its cytotoxic nature. Monobenzyl ether of hydroquinone (MBEH) and monomethyl ether of hydoquinone (MMEH) also demonstrate tyrosinase inhibitory properties Generation of free radicals causes melanocyte loss. However, the use of these compounds for depigmentation is limited by their adverse effects.

Arbutin is a naturally occurring ??, D ' glycolpyranoside derivative of hydroquinone. It does not affect RNA synthesis although it shows tyrosinase inhibition. The ??-derivative shows a stronger inhibitory effect on tyrosinase and melanosome maturation. It is also present in many of the botanical extracts. It is highly pH-sensitive and can hydrolyze to hydroquinone at both acidic and alkaline pH. Hence, care should be taken during use in commercial skin-lightening products.

Kojic acid is a powerful tyrosinase inhibitor having functions by the chelating of copper at the active site of the enzyme tyrosinase. It acts as an antioxidant and a free radical scavenger. Although powerful, due to its adverse side effects such as allergic dermatitis, the use of kojic acid is under inspection by dermatologists. It is found to be unbalanced in formulations and may also cause discoloration. Since it penetrates the skin, a demand for safe and effective alternative botanicals is there as preferred skin-lightening ingredients.

4.2.2 Botanical extracts
Extracts mostly contain a combination of two or more classes of compounds that work synergistically to achieve skin lightening. Botanicals are available from nature and are thus 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 is observed that natural extracts may be highly unstable and may not be compatible within formulations. The products are available commercially through suppliers for use as skin-lightening agents.

4.2.3 Antioxidants
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, thereby 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 which is one of the major causes for tanning. Although antioxidants are present in tissues, they may not be able to reduce the radicals, depending on the extent of UV exposure. Inflammation is a source of free radicals. Hence the quenching of free radicals would also help in reducing the synthesis of melanin, thereby contributing to skin depigmentation effects. Due to their strong antioxidant nature, phytic acid, glutathione, and ubiquinone are used as popular skin-lightening agents. Melanin synthesis in melanocytes is accompanied by the generation of hydrogen peroxide that leads to the formation of ROS that further increase the production of melanocytes.

4.2.4 Vitamins
Vitamins have been known to improve skin tone and texture, and they have found noteworthy 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 Kligman's treatment. It is used along with hydroquinone and topical steroids for the treatment of melasma. Tretinoin acts as a skin-lightening agent by inducing exfoliation. Further, it accelerates the loss of epidermal melanin by increasing the turnover rate thereby promoting the proliferation of keratinocytes. However, side effects such as burning and increased photosensitization are observed. 'Retinyl palmitate', a derivative of retinoic acid, is used in skin-lightening cosmetic preparations.

Among the classes of vitamins that comprise vitamin B, two have been identified to have skin-lightening activity. Vitamin B3 (niacinamide) is one of the widely used hypo pigmenting agents. It is a well known antioxidant and interferes in melanasome transfer leading to skin lightening. Investigators have depicted that niacinamide inhibits the transfer of melanosomes from melanocytes to keratinocytes using co-cultures of human melanocytes and keratinocytes. The results of clinical studies using topically applied niacin amide have demonstrated a reversible reduction in hyper pigmented lesions thus inducing skin lightness. Vitamin B5 (panthenoic acid), a derivative of vitamin B5, calcium pantetheine sulfonate has been observed to interfere with the glycosylation of tyrosinase, thus leading to depigmenting effects.

Vitamin C is required for the production of collagen and is a photoprotectant. It deactivates UV-induced free radicals and decreases erythema. Further, Vitamin C also acts as a tyrosinase inhibitor, thereby lightening the skin. Although most efficient, ascorbic acid is a highly unstable compound. Stable derivatives of ascorbic acid in the ascorbyl palmitate are widely used in cosmetic products.

Vitamin E is the most important lipid-soluble antioxidant in the body. It is copious in the sebum which acts by absorbing the oxidative stress of sunlight and skin exposure. It has been demonstrated that vitamin E provides protection against UV-induced inflammation and hyper pigmentation. This vitamin has also been studied in combination therapies with other vitamins as well as in other classes of skin-lightening compounds. Vitamins B, C, and E are incorporated individually or in combination in many skin-lightening treatment therapies.
4.2.5 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 to affect melanin and melanosome ingestion by human keratinocytes. The protease activated receptor-2 regulates 'keratinocyte phagocytosis'. The peptide-based antagonist for PAR-2 can be used to regulate melanin ingestion by keratinocytes. Short peptides have also been reported in reducing the enzymatic activity of tyrosinase. A high-molecular-weight soluble glycoprotein from silk i.e. sericin, is used as a tyrosinase inhibitor. Peptide residues that act as MSH inhibitors have been known to lighten the skin. Soy trypsin inhibitors have been identified as interfering in melanosomal transfer, thereby reducing skin pigmentation.

4.2.6 Alpha and Beta hydroxyl Acids (AHA)
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. They are comparatively pure and economical, and they may be used in higher amounts without many side effects. They are generally used in conjunction with other skin-lightening agents to progress the performance. Also referred to as fruit acids, they improve skin texture by promoting desquamation or the shedding of the outer layers of the stratum corneum. Alpha hydroxyl acids (AHA) have also been well-known to increase the enzymatic activity leading to epidermolysis. They are also engaged in micro dermabrasion techniques. They act as moisturizers and promote the synthesis of elastin fibers, leading to enhanced skin tone. However, care should be taken to neutralize the skin after AHA treatment as it causes burning and erythema. The most commonly used AHAs are glycolic, lactic, citric, malic, pyurvic and salicylic acids and their derivatives.

Figure 5: Mechanisms of current cosmeceutical agents like Alpha-hydroxy acid (AHA)
4.3 Efficiency of Skin Whitening agents
Formulations for skin lightening have been majorly based on o/w emulsions that have a higher artistic appeal. The fact that many of the ingredients get better dispersions is also an added feature for the choice of such emulsions. For suitability in certain skin types, recently gel-based formulations are being considered. Efficacy studies for skin-lightening formulations are carried out through clinical trials. Some of the techniques involves the use of the mexameter, chromameter, spectrophotometer and VISIA, along with dermatologist assessment. Also other skin parameters such as moisturization, texture, barrier integrity, pH etc are being evaluated to give picture of skin health after the use of skin-lightening agents. This leads to screening the potentially dangerous side effects of hydroquinone-like substances. It is becoming easier to identify the efficacy of formulations in different skin types with advances in technology in the measurement techniques.
4.4 Skin Anti aging agents

Figure 5: Properties and benefits of Anti aging agents in cosmetics
Skin aging is a complex biological process influenced by combination of endogenous or intrinsic (genetics, cellular metabolism, hormone and metabolic processes) and exogenous or extrinsic (chronic light exposure, pollution, ionizing radiation, chemicals, toxins) factors. These factors show cumulative structural and physiological alterations and progressive changes in each skin layer as well as changes in skin appearance, particularly on the sun-exposed skin areas. In contrast to thin and atrophic, finely wrinkled and dry intrinsically aged skin typically shows a thickened epidermis, mottled discoloration, deep wrinkles, laxity, dullness and roughness. Gradual loss of skin elasticity leads to the phenomenon of sagging. Slowing of the epidermal turnover rate and cell cycle lengthening coincides with a slower wound healing and less efficient desquamation in older adults. On the other side, many of these features are targets to product application or procedures to accelerate the cell cycle, in the belief that a faster turnover rate will yield improvement in skin appearance and will accelerate wound healing. A marked loss of fibrillin-positive structures as well as a reduced content of collagen type VII (Col-7), may contribute to wrinkles by deteriorating the bond between dermis and epidermis of extrinsically age skin. Sun-exposed aged skin is characterized by the solar elastosis. The thin distribution and decrease in collagen content in photoaged skin can be due to increased collagen degradation by various matrix metalloproteinases, serine and other proteases irrespective of the same collagen production. In older skin, collagen looks irregular and disorganized. The ratio of Col-3, to Col-1 has been shown to increase significantly to a loss of Col-1.29. The overall collagen content per unit area of the skin surface is known to decline approximately 1% per year. Glycosaminoglycans (GAGs) are the primary dermal skin matrix which helps to bind the water. In photo-aged skin, GAGs may be associated with abnormal elastotic material and thus be unable to function effectively. The total hyaluronic acid (HA) level in the dermis of skin that age fundamentally remains stable however, epidermal HA diminishes markedly. The three primary structural components of the dermis i.e. collagen, elastin and GAGs have been the subjects of the majority of anti-aging research and efforts for aesthetic anti-aging strategies pertaining to the skin from 'anti-wrinkle creams' to various 'filling agents' are developed time to time. Due to aging, the entire face is associated with the gravity impact, muscles action, loss of volume, diminishing and redistribution of superficial and deep fat and loss of bony skeleton which altogether leads to face sagging, changes in skin tightness and contour.

4.5 Classification of Anti aging agents

There are three main groups of agents that can be used as anti-aging cream components, the antioxidants and the cell regulators. The antioxidants such as vitamins, polyphenols and flavonoids decrease collagen degradation. The cell regulators such as retinols, peptides and growth factors (GF) have direct effects on collagen metabolism and influence collagen production.
4.5.1 Antioxidants as anti aging agents
Vitamins C, B3, and E are the most important antioxidants because of their ability to penetrate the skin due to their low molecular weight. The water-soluble, heat-labile local L-ascorbic acid having concentrations 5 - 15%, enzymes for the production of collagen, and inhibitors of matrix metalloproteinase (MMP), were proven to have a skin anti-aging effect by inducing the production of Col-1 and Col-3. Various clinical studies have also proven that the anti oxidative shield is higher with the combination of vitamins C and E rather than the vitamins alone. Niacin amide (vitamin B3) regulates cell metabolism and regeneration and is used in 5% concentration as an anti-aging agent. In some studies, improvement of skin elasticity, erythema and pigmentations after topical treatments have been observed. Vitamin E (??-tocopherol) used in concentrations 2 - 20% as a constituent of skin products has anti-inflammatory and anti proliferative effects. It promotes smoothing of the skin and increases the ability of the stratum corneum to maintain its humidity.

4.5.2 Alpha hydroxyl Acids (AHA)
Alpha-hydroxyl acids (AHAs) may be seen on cosmetic product labels as glycolic acid, lactic acid, malic acid, citric acid, alpha-hydroxycaprylic acid, hydroxycaprylic acid, alpha-hydroxyethanoic acid, alpha-hydroxyoctanoic acid and some hydroxyl fruit acids. The most generally used alpha hydroxyl acids in cosmetics are glycolic acid and lactic acid. The Food and Drug Administration (FDA) provides certain limits where AHA can be used within 10% of concentration. AHA reduces the stratum corneum by decreasing the rate of corneocyte cohesion and increasing the speed of normal process of skin cell regeneration and exfoliation. At higher concentrations of 25% AHAs can cause increase in epidermal or papillary dermis thickness, increase in acid mucopolysaccharides, improved quality of elastic fibers and improved collagen density. Gene expression of collagen and hyaluronic acid in the dermis and epidermis is also promoted. The degree of exfoliation is comparative similar to the duration of application and higher concentrations of acids have more intoxicating anti-aging effects. A study comparing 5% and 12% lactic acid found that application of 12% lactic acid twice daily for 3 months resulted in improved epidermal and dermal firmness and thickness with clinically improved skin smoothness and appearance of lines and wrinkles. With 5% lactic acid there was no modulation of the dermis.
4.5.3 Cell regulators
Cell regulators such as vitamin A derivatives, polypetides and botanicals act directly on the collagen metabolism and stimulate the production of collagen and elastic fibers. Vitamin A (retinol) and its derivatives which include retinaldehyde and tretinoin are also a group of agents with antioxidant effects. They induce biosynthesis of collagen and reduce the expression of MMP 1. Retinol causes less skin irritation in comparison of tretinoin in skin aging products. Tretinoin, having a strong positive effect on collagen metabolism is a non aromatic retinoid of the first generation which is approved for function as an anti-aging treatment in a concentration of 0.05% in the USA. It reduces the signs of UV-induced early skin aging such as wrinkles, loss of skin elasticity and pigmentation. Through topical application, polypeptides encourage collagen synthesis and triggers dermal metabolism.
4.6 Efficiency of Anti Aging agents
The mainspring of any skin anti-aging therapy is to achieve a healthy, soft, blemish-free, lucid and supple skin. In clinical practice, patients should be orientated to the treatment modality that gives the most rewarding results. Before choosing the strategy for any individual case, age, previous surgeries, general health statuses, type of the skin, lifestyle and many other factors should be concerned. The preferred therapeutic anti-aging effect of the skin is unremitting and step-by step process which combines the skin bio-revitalization and rejuvenation, augment intensification and renovation of each skin layer separately.
4.7 Skin Thickening agents
These two types of thickeners provide two important differences in performance:
' The flow behaviour
' Temperature dependence of the viscosity.

Figure 6: Thickeners for the surfactant system modifying micelle structure

Basically, the thickening agents modify the micellar structure. In case of the polymeric hydrophilic thickeners, the hydrophobic groups of the molecules are included into the surfactant micelles. This leads to bridging of the spherical micelles and an increase of the micelle size by the PEG-chains. Now the micelles have more limited space to be in motion which leads in an increase of viscosity and a Newtonian flow behavior. The hydrophobic thickeners are also incorporated into the surfactant micelles, but since their hydrophilic head group is quite small, they change the shape of the micelles. The shape changes from spherical into rod-like. At rest, the micelles are arranged randomly which leads to a high viscosity. With increasing shear rate, the micelles get oriented parallel and hence the viscosity decreases. This process is reversible with decreasing shear rate while the viscosity increases when the micelles are arranged randomly again.

4.8 Classification of Thickening agents

4.9 Efficiency of Skin Thickeners
By choosing the right thickening agents one can achieve:
' A good consumer acceptance of the final product.
' Good stabilizing effects.
' A reduction of the temperature dependence of the viscosity.
' A reduction of the total amount of thickener due to synergistic effects.
' Additional benefits like conditioning, moisturizing, refatting, and solubilizing.
4.10 Skin Anti Acne agents
Acne vulgaris is a universally occuring disease which affects the pilosebaceous follicles. It s caused due to the relationship of four pathogenic factors i.e. sebum production, follicular hyper keratinization, microbial colonization by the bacteria acnes and the release of inflammatory mediators into the follicle and dermis. Acne initiates when increased amounts of adrenal androgens causes swelling of the sebaceous glands and enlarged production of sebum on the face, chest, and back in the pre-pubertal period. The severity of acne is often associated with the amount of sebum produced. In the acne affected follicles, there is an increased desquamation of follicular keratinocytes and the corneocytes experience cohesive nature because of a changed pattern of keratinization. As a result the follicular obstruction by the combining sebum and desquamated epithelial cells helps in the formation of a 'microcomedone': the originator lesion of acne.
4.11 Classification of Anti Acne agents

' Tretinoin
The topical tretinoin i.e. trans retinoic acid is a highly efficient comedolytic agent. It normalizes follicular keratinization, promotes drainage of pre existing comedones and inhibits the formation of newer ones. Due to inhibition of micro comedone formation, it diminishes in inflammatory lesions. Clinical improvement of a maximum extent may be apparent after three to four months of usage. Tretinoin is useful in mono therapy for non inflammatory acne or mild to moderate inflammatory acne. It has also been used efficiently when combined with topical antibiotics, benzoyl peroxide or systemic antibiotics, presumably as of its ability to increase the penetration and to improve the efficiency of other agents. Also there is an apparent decrease in the irritation from tretinoin by the addition of a topical antimicrobial agent which is beneficial. The most common undesirable effect associated with tretinoin preparations is that it induces irritation. Patients also experience erythema, dryness and peeling if the prevalence increases which often resolves after around three weeks.

' Topical Antibiotics
They are helpful in the treatment of moderate inflammatory acne by reducing the amount of acnes in sebaceous follicles thereby demonstrating anti-inflammatory properties by suppressing chemotaxis and declining the percentage of pro-inflammatory free fatty acids in surface lipids. Erythromycin, clindamycin, sodium sulfacetamide and salicylic acid are some of the examples of topical antibiotics. These are frequently used effectively in combination with BPO or tretinoin. Since many years, an antibacterial agent named 'sodium sulfacetamide' has been used in anti acne preparations. Recently it is offered in combination with sulfur (5%). Application of all topicals should be done on the entire face rather than to individual lesion.

' Erythromycin
Resistance of acne to erythromycin seems to be more familiar than that produced by tetracyclines. Oral erythromycin is compared to tetracycline in its therapeutic effect on acne though the most general adverse effect associated with erythromycin is GIT (gastro intestinal tract) irritation which may be alleviated to some extent by taking the drug along with eatables.
' Adapalene
It is a synthetic naphthoic acid derivative with retinoid activity having a markedly different chemical structure from tretinoin and interacts with a unique set of receptors. It is a powerful modulator of cellular differentiation, keratinization and inflammatory processes having mechanism of action similar to other retinoids. Interestingly, adapalene acquires moderate to potent anti-inflammatory activity when compared with corticosteroids and non steroidal anti-inflammatory drugs in several in vitro and in vivo preclinical studies. In the some models, tretinoin and isotretinoin were found to have either weak or no anti-inflammatory activity. Several clinical studies have demonstrated that 0.1% gel constitution of adapalene is more effective than 0.025% tretinoin gel in decreasing the number of acne lesions.
4.12 Newer Anti acne agents
Since past few years, several new agents like new retinoid, new tretinoin formulations, azelaic acid, a new formulation of sodium sulfacetamide and an oral contraceptive having a second generation progestin.

4.13 Efficiency of Anti acne agents
The new topical retinoids are at the most equivalent in value compared with the existing preparations. More prominently, these agents are advantageous over existing topical retinoids in declining local irritation. Local irritation is the most common adverse effect associated with existing topical retinoids and results in discontinuation of therapy or other compliance problems. The newer agents thus improve compliance and consequently are the result of the success of therapy. They are most suitable for patients with mild to moderate comedonal and mixed inflammatory acne. Clinical experience may help state the proper choice for ceratin patients.

4.14 Skin Moisturizing agents
The idiom 'moisturizer' is a specific marketing term which is used by the consumers who consider moisturizers which help in actively increasing the water content of the skin. Dermatologists perceive moisturizers as bland oleaginous substances that are applied to the skin by rubbing and massaging on the skin. Here it does not necessarily involve that moisture or water is being added to the skin. When there is a modification of the epidermal barrier and reduced water content in the epidermis, moisturizers are used as a main component of basic skin care. They restore the barrier function of the epidermis inorder to wrap tiny fissures in the skin thereby providing a soothing shielding film and increase the water-content of the epidermis. Thus there is a slow evaporation process of the skin's moisture thereby maintaining hydration and tactile properties of dry skin. Dryness can cause the skin to appear discolored, flaky and rough. The stratum corneum (SC) contains corneocytes seized together by a lipid bilayer. Lipid membranes comprises of cholesterol and free fatty acids and also ceramides which restrict transepidermal water loss (TEWL) and uphold the skin barrier. Corneocytes consists of water soluble molecules called natural moisturizing factors (NMF) that allows the skin to bind with water. The combined action of water binding and water loss prevention maintains skin hydration and allows the stratum corneum to be supple and stretchy.
4.15 Types of Moisturizing agents

' Humectants
These substances help in water attraction by two different ways. One is by enhancing water absorption from the dermis into the epidermis and second is helping the stratum corneum (SC) to absorb water from the environment in humid conditions. The most effective humectant is the tri-hydroxylated molecule, glycerol. Immature corneocytes are brittle but mature into more flexible and defensive cells as they migrate through the SC. Glycerol reduces the scaling associated with xerosis by inducing the digestion of desmosomes and later enhancing desquamation. Pyrrolidine carboxylic acid found in the NMF, hydrates the skin by improving xerosis. Urea is another significant humectants. In double blind studies moisturizers containing urea shows a reduced amount of TEWL in ichthyotic patients. Alpha hydroxy acids are useful agents for the treatment of dry skin. Lactic acid particularly the L-isomer, stimulates 'Ceramide biosynthesis' leading to higher ceramide levels that result in a higher lipid barrier and more resistance against xerosis. Limitations of humectants include the boost of TEWL by enhancing water absorption from the dermis into the epidermis where it can be vanished into the environment. Ingredients of occlusives and humectants are combined to increase epidermal hydration and barrier function.

' Emollients
These are the lipids and oils which hydrate and improve the appearance of the skin by causing skin smoothness and enhanced elasticity. Consumers desire smooth skin after moisturizer application hence emollients are used to fill the cracks between clusters of desquamating corneocytes. In pharmaceuticals and cosmetic formulations, long chains of saturated fatty acids and fatty alcohols are normally used. Their beneficial effects are evident while improved repair and on permeability. Examples include stearic acid, linoleic acid, linolenic acid and oleic acid present in palm oil, coconut oil and wool fat. The visible symptoms of Sodium lauryl sulphate (SLS) induced irritation is reduced by a sterol enriched portion from canola oil. Other lipids like fish oil, petroleum, shea butter, and sunflower seed oil showed zero effect on the degree of irritation. Skin physiology is influenced by the essential fatty acids like linoleic acid and alpha linoleic acid via their effects on processes like skin barrier functions, eicosanoid production, membrane fluidity and cell signaling.

' Occlusives
These are the substances which reduce TEWL by creating a hydrophobic barrier over the skin and contributing to the matrix between corneocytes and have the most marked effect when applied to faintly dampened skin. There is a wide range of agents with occlusive properties. Their main restrictions include poor odor, potential allergy and the slippery feel. Petroleum jelly, with a concentration of 5%, reduces TEWL by more than 98% while dimethicone reduces TEWL by only 20% to 30%. Occlusives diffuse into the intercellular lipid domains which show their good efficiency. Petroleum is broadly used as a classic moisturizer. Other examples are lanolin, lanolin alcohols, lanolin acids, a complex structure of esters, hydroxyl esters of high molecular weight
4.16 Efficiency of moisturizing agents
' TEWL is prevented by effective hydration of the stratum corneum
' Smooth and supple skin appearance
' Lipid barrier restoration i.e. enhancing the skin's NMF preservation mechanisms
' Elegantly accepted in cosmetics
' Good moisture content for sensitive skin
' Hypoallergenic and non sensitizing
' Loss of fragrance
' Affordable which lasts long
' Hydrates immediately thus absorbed thoroughly

Figure 7: Examples of humectants, emollients and occlusives as moisturizering agents
4.17 Skin Tanning agents
These agents are the chemicals applied to the skin to produce an effect which appears identical to a suntan. Since the 1960s, the popularity of sunless tanning has rose after relations were made by health authorities between exposure to the sun and other sun tanning methods such as sun beds or tanning beds. Certain antioxidants like carotenoids are found in some fruits and vegetables such as carrots and tomatoes which is a safe and effectual method of sunless tanning. This results in changes in skin color when taken in high amounts. Carotenoids are long-lasting and have been linked to more attractive skin tone than suntan. They also fulfill the function of melanin in absorbing the UV radiation and protecting the skin. Several tanning agents are available such as DHA based and Tyrosine based products, melanogenesis stimulants and temporary bronzers.

Figure 8: Pie chart depicting recent sales of various cosmetic products (in %)

Figure 9: Core message of clinical trials on cosmetics
4.18 Introduction to clinical trials :
Ethical considerations are a vital part of any biomedical research involving human subjects. Medical research is a research conducted to increase the knowledge in the field of medicine. It can be divided into two main categories i.e. basic science (non therapeutic or non clinical) medical research and applied science (therapeutic or clinical) medical research. The first one principally involves healthy persons and is approved to increase the understanding of fundamental principles thus contributing to the applied clinical research. The second one involves sick personnel and is proposed to evaluate a new diagnostic or therapeutic method for safety and efficacy. Studies involving skin measurement methods and testing of cosmetic products on humans are similar to medical research. Research subjects involve human beings dealing with pure scientific research, whose chief purpose is to contribute to widespread knowledge about the human skin physiology and active substances and with this applied research it is aimed to evaluate the safety and efficacy of new cosmetic ingredients and finished products. In both studies, the moral considerations are related to the relationship between the physician and the human subject that is the healthy or sick volunteer. Their key purpose is to protect the human beings thereby following the guidelines for Good Clinical Practice (GCP) integrated into the design of the research.

4.19 Key Messages for Performing an Ethical Study
' Favorable assessment risk
' Systematic study design
' Chosen and learned consent
' Research subjects selection options
' Fair approval by IRB/IEC
' National and international regulations and standards

4.20 Researches on Anti-aging Cosmetic products
' In vivo patch study
Dermatologists at The University of Manchester carried out clinical trials on 60 volunteers with typical signs of sun-damaged skin and found that the cosmetic, No7 Protect & Perfect Intense Beauty Serum could improve skin aging problems.
The study showed that 70% of individuals using the beauty product had significantly fewer wrinkles after 12 months of daily use compared to volunteers using a placebo.
It was found out that the serum stimulated the production of fibrillin-1, a protein that promotes elasticity in the skin but research is still going on as it has been confirmed with prescription retinoids. There is slight evidence that overabundance of cosmetic 'anti-ageing' products can produce similar effects although prescription retinoids can have a reparative effect on photo-aged skin. The clinical trial was carried out using standard scientific protocols with 60 volunteers who included 11 men and 49 women aged 45 to 80 years being recruited for testing the efficacy. There was no awareness among the investigators and the volunteers as these products were supplied in matching and coded packages. Thirty volunteers were assigned the No7 Protect & Perfect Intense Beauty Serum and the rest thirty used the placebo formulation. The studies demonstrated that the cosmetic can produce significant improvement in the appearance of facial wrinkles along with its long term usage.
' Randomized controlled trial
Sixty healthy but photo aged volunteers were recruited to this study that included 11 men, 49 women aged 45 to 80 years. All test products were supplied in identically packaged and coded containers so that the investigators and subjects were unaware as to the treatment. There was a random selection for the allocation of the subjects for their self treatment with the vehicle formulation or the test product. The regulations for its use included daily evening application to the entire face and dorsa of the hands with wrists and extensor forearm for 6 months. Clinical assessments of the skin were performed for all participants at baseline and for the coming one, three and six 6 months of product use. The following four parameters were assessed at each visit i.e. fine lines and wrinkles, dyspigmentation, overall clinical grade of photo ageing and tactile roughness. The scale of these parameters ranges from 0 to 8, where 0 represents zero evidence of photo ageing and 8 represents the most severe photo ageing. Pigment was assessed on a similar 0'8 scale, where 0 denotes a uniform coloration of the skin with absence of photoageing-related colour change and 8 represents severe dyspigmentation. Similarly, in tactile roughness 0 represents totally smooth skin with no rough patches and 8 represents very roughened skin.

Statistical Analysis Final Results
In vivo patch study Randomized controlled trials In vivo patch study Randomized controlled trials
Differences in the stains produced by the vehicle and test product were assessed for
consequence usage of the repeated measures of Analysis of Variance
(ANOVA) In order to assess the six months data, analysis of covariance (ANCOVA) was performed using the baseline for Linear regression analysis which was used to extrapolate the vehicle response to 12 months.
The final twelve months clinical assessment data were analyzed using a combination of Wilcoxon's matched pairs. A significant deposition of fibrillin-1 in the papillary dermis was observed. However, it resulted in a significant deposition of fibrillin-1, thus having similar accumulation to that of vehicle formulation i.e.
1??70 ?? 0??17; test product 2??64 ?? 0??22.
Also the 15 treatment with RA had little effect on evidence of MMP-1 in the epidermis After six months, the test product showed significant
improvement in facial wrinkles as compared to baseline assessment whereas vehicle-treated skin was not treated. 43% of the subjects having test product depicted an improvement in facial wrinkles, 22% having vehicle depicted improvement compared with baseline. After 12 months benefit of test product as compared to the vehicle where 70% whereas 33% improved combined with Wilcoxon rank tests.

Table 6: Statistics and results of anti aging agents performing various studies
4.21 Researches on Skin Whitening products
Skin-whitening is the practice of using artificially created chemical substances to physically lighten one's skin tone by reducing the concentration of the primary determinant of skin color, melanin. The brown-black pigments are found in melanocytes which are the skin cells found on the bottom layer of the skin's epidermis. These pigments are derived from tyrosine, an amino acid that plays an integral role in the photosynthesis process to convert light energy into chemical energy for use within the body. Differences in skin color are due to the melanocyte's activity levels, which are regulated by the body's hormones. The common active ingredients found in skin-whitening creams are hydroquinone and kojic acid. These chemical compounds lighten the skin by eliminating melanocyte activity. Many global beauty care and cosmetics companies outsource their chemical compound manufacturing processes to third-party contractors in China and East Asia, including the production of hydroquinone and kojic acid for skin-whitening creams. This outsourcing practice has helped stimulate the economy and increase consumer purchasing power. There are two main approaches that global cosmetics companies utilize to advertise to their Taiwanese consumers i.e. a scientific approach and a symbolic approach. The scientific approach is a modernist way of framing skin-whitening products to users, utilizing the skin-whitening is the practice of using artificially created chemical substances to physically lighten one's skin tone by reducing the concentration of the primary determinant of skin color, melanin. Melanin-containing cells are located in the bottom layer of the epidermis section of the skin, an anchoring point for the outer skin to the rest of the inner flesh. In order for topical skin-whitening creams to reach this layer, they must penetrate past the four outermost layers of skin. Each layer's thickness is equated to be roughly the thickness of a single sheet of paper. Though four sheets of paper stacked together seems relatively small to the human eye, viewing this on a microscopic level highlights the impressive journey that these chemical compounds take to make their attack against the melanin. These skin whitening chemical compounds penetrate our body's largest natural defense mechanism, the skin which is an excellent example of society's traumatic means of achieving aesthetic beauty ideals. However, the average consumer is not aware of this trauma's extent because of the ability of advertised symbols and messaging to spin the process in a positive light as a revitalizing and corrective practice.

Skin-Lightening agents In Vitro studies In Vivo studies
Hydroquinone Tyrosinase activity, melanin inhibition and cellular metabolism is inhibited by affecting both DNA and RNA syntheses Reduced pigmentation in melasma patients
Arbutin Tyrosinase activity and melanin production is inhibited, with DOPA oxidase activities Overall skin lightness and improved solar lentigines after twelve week treatment
Kojic Acid/Kojic acid
tripeptides Catecholase activity of tyrosinase is inhibited, and comparative studies with kojic acid tripeptides and unconjugated kojic acid is carried out Similar results shown by the comparative study on skin lightening effect of hydroquinone and kojic acid
Azelaic acid Melanin inhibition in cells of melanoma Patients with facial hyper pigmentation improved in pigment intensity by one or more grades also comparative study showed 20% azelaic acid more efficient than 2% hydroquinone in patients with melasma
Aloesin Tyrosinase, tyrosine hydroxylase and DOPA oxidase were inhibited and data showed synergistic action with arbutin Suppressed pigmentation by 34% in lower forearm
Resveratrol Reduction in MITF and tyrosinase supporter activities Treatment with dark-skinned Yucatan swine showed visible skin lightening
Glabiridin Inhibition of both mono- and diphenolase tyrosinase activities 90% of the patients showed good to excellent results in the trials for melasma treatment
Soyabean Inhibition of protease-activated receptor 2 cleavage, affects cytoskeletal and reduces keratinocyte phagocytosis Photo damage studies showed more efficient effects than the vehicle in improving mottled pigmentation
Niacin amide 35'68% inhibition of transfer of melanosome in the co-culture model Fine lines and wrinkles, hyper pigmentation spots, texture and red blotchiness was reduced
Retinoic acid TRP-1 protein was inhibited with melanin synthesis Lighter pigmentation
in 68% of the patients
Vitamin C
Melanin formation on purified tyrosinase was suppressed 19 of 34 patients lightens with chloasma or senile freckles
Octa - decenedioic acid Tyrosinase mRNA and protein expression were reduced with melanogenesis Even skin tone and overall lighter skin colour

Table 7: In vitro and in vivo study results of skin whitening agents

5.1 Conclusion
The escalating therapeutic options shown by cosmeceuticals include a wide range of compounds of various biochemical functions. Constant 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 in anti aging products also. Recent scientific studies have led to encouraging results in the cross application for wound healing and their biological activity to promote neocollagenesis and synthesis of other extracellular matrix components for modulating the inflammatory response to the skin. A thin line distinguishing hype and optimism providing better clarity and overview of the process of manufacturing of skin cosmetics, should allow all interested practitioners to make evidence based decisions. Although further studies are clearly warranted, awareness of the effects of cosmetic agents will provide yet another tool in the treatment of physicians actively seeking to improve patient care and outcomes. However, it remains to be investigated whether regulation of newer cosmetic products in market could evolve in potent and safe skin related regimes for future use. Cosmetic products must be safe for all potentially susceptible populations likely to purchase or use such products unless a specific user group is clearly defined by a special management of the product. Also, the performance, position and claims of a cosmetic product can selectively deal with or eliminate certain consumer groups. A safety assessment must be taken into account for these groups.

5.2 Future Perspectives
The inspiration that cosmetics are a kind of technology which contains a testable hypothesis that is effective for cosmetics could be improved through the application of scientifically exposed factors of beauty. In the beginning of the 21st century, analysis of the trends present in the global cosmetics market leads to the some significant conclusions. The demand for cosmetics will keep budding, fueled mostly by the emerging markets of Asia and Latin America which will contribute to foundation of new products. It will shape new spending patterns and possibly even establish new beauty canons.
Global cosmetics manufacturers will have to distinguish their products in order to adjust them to the expectations of their new consumers, originating from different non-western cultures and behaving differently. Skincare is the fragment with the biggest growth potential. The flagship part on the cosmetic market will pertain over the next few years. The deciding factor for market success will be mass cosmetics sales which will set the tone for the entire market.
The distribution structure is changing with supermarkets and hypermarkets as well as online sale channels being increased with their shares on the whole market. New product launches are based on an increasing way of advanced research and technologies. On the other hand, there is a growing demand for organic products manufactured in a sustainable way, often according to the fair trade philosophy.

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