BACKGROUND
Until the beginning of the 1900s, no cleardifference existed between active and inactive components in dermatological andcosmetic preparations. Later, it became possible to assign specific therapeuticeffects to certain chemical substances, and the concept of vehicle, i.e., arather inactive carrier substance, started to be developed. Nowadays,formulations are mixtures of components that basically include one or morevehicles and one or more active principles. The efficacy of dermatological andcosmetic products is influenced by the type of vehicle and active principles.In general, formulations will work if the active ingredients penetrate into theepidermis. Hence, the correct selection of a suitable vehicle plays animportant role during the development of a product. Pharmaceutical preparationsare aimed at obtaining a curative effect. In these cases, the role of thevehicle is primarily to allow the delivery of the active principles to the siteof application. Cosmetic formulations do not contain strictly curative drugs,but their purpose is rather to help skin homeostasis and prevent degenerativeprocesses. As we have seen, a clear boundary between the medical and cosmeticfields cannot be easily traced, while the marked tendency of cosmetic industriesto develop products containing pharmaceutically active principles has led tothe introduction of the concept of cosmeceuticals. This term indicatescosmetic-pharmaceutical hybrids aimed at enhancing the beauty of the skin bymeans of ingredients that modify skin functionality or provide additionalhealth-related function or benefit.
The outer layer of the epidermis, theexternal layer of human skin, is made up primarily of corneocytes which providea barrier function. Underlying the corneocytes are viable keratinocytes, whichmigrate outward and terminally differentiate to become corneocytes. Theepidermis is organized into extensions called rete ridges that project betweendermal papille (pink) into the underlying connective tissue. Underlying theepidermis is the dermis, which is primarily made up of collagen, elastinfibers, and other extracellular matrix components. Collagen and elastin fibersare synthesized by fibroblasts to provide tensile strength, firmness, andelasticity to the skin. The innermost layer of the skin, the hypodermis, iscomposed largely of fat cells, which helps provide structure to the skin. Bloodcapillaries, lymph vessels, sweat glands, sebaceous glands, hair follicles andlamellar bodies lie within the dermis and hypodermis (Figure 1).
INTRODUCTION Now, a variety of skincare products are available for almost any beautyconcern one can have, including body washes, gels, lotions, exfoliants,moisturizers, toners and sun protection. There is mainly a focus on helpingskin from the inside out. The existence of the FDA keeps known toxicingredients from being used, though many skincare products still dounfortunately have side effects. From time immemorial creams as, topicalpreparations are considered an important part of cosmetic products. Creams maybe considered pharmaceutical products as even cosmetic creams are based ontechniques developed by pharmacy and un-medicated creams are highly used in avariety of skin conditions in ancient times, creams were simply prepared bymixing of two or more ingredients using water as the solvent. With theadvancement in technology, newer methods are used for formulation of creams.These semisolid preparations are elegant to use by the public and society. Theyshow versatility in their functions. Creams can be applied to any part of thebody with ease. It is convenient to use cream by all the age group of people.Although it may be equally well applied to non-aqueous products such aswax-solvent based mascaras, liquid eye shadows and ointments. If an emulsion issufficiently low viscosity to be pourable (flow under influence of gravityalone) is referred to as lotion. Creams are emulsions of oil and water. Incoming future, more advanced technologies and methods will be used forpreparation, formulation and evaluation of creams. Also, the demand of herbalconstituents-based creams is increasing day by day. SKIN CARE PROCEDURES AND SKIN CARE PRODUCTS The information of skincare procedures is plentiful but little scientifically documented and thenumber of products available for cleansing, soothing, restoring, reinforcingand protecting is of an almost infinite variety. Nonetheless theirfunctionalities may be described as: ·Removal of dirt, sebum, microorganisms,exfoliated corneocytes and other non-wanted substances from the skin. ·Reduction of unpleasant skin symptoms(e.g. pruritus, burning, odor). ·Restoration of (sub-clinically) damagedskin (e.g. dry and inflamed skin). ·Reinforcement of undamaged butvulnerable skin (e.g. skin surface pH balance, germ reduction). ·Protection of damaged, undamaged andvulnerable skin from various noxious factors. ·Providing a pleasant skin feel(well-being) [1]. Maintaining the functional integrity of the stratumcorneum It has been recognized for approximately 7decades that the stratum corneum exhibits biological properties that contributedirectly to maintaining and sustaining healthy skin. Continued basic scienceand clinical research coupled with keen clinical observation has led to morerecent recognition and general acceptance that the stratum corneum completesmany vital “barrier” tasks, including but not limited to regulating epidermalwater content and the magnitude of water loss; mitigating exogenous oxidants thatcan damage components of skin via an innate antioxidant system; preventing orlimiting cutaneous infection via multiple antimicrobial peptides; respondingvia innate immune mechanisms to “cutaneous invaders” of many origins, includingmicrobes, true allergens, and other antigens; and protecting its neighboringcutaneous cells and structures that lie beneath from damaging effects ofultraviolet radiation. Additionally, specific abnormalities of the stratumcorneum (Figure 2) are associatedwith the clinical expression of certain disease states [2]. The corneocytes represent the bricks and theintercellular lamellar lipid membrane represents the mortar. Corneocytescomprise primarily keratin macrofibrils, are protected externally by acornified cell envelope, and are held together by corneodesmosomes. Theintercellular lamellar lipid membrane is primarily composed of ceramides,cholesterol, and fatty acids. A mixture of multiple small hygroscopic compoundspresents within corneocytes, referred to collectively as natural moisturizingfactor (NMF), plays a vital role in the physiological maintenance of stratumcorneum hydration. The functionality of the skin care productsranges from mono-functional, e.g. protecting barrier creams to poly-functional,e.g. soothing and restoring cleansers. They unfold their functionality asleave-on products (e.g. moisturizing or skin barrier products), or as rinse-offproducts (e.g. cleansers). Skin care procedures like washing/drying and theapplication of leave-on products should be as benign as possible. The undulyremoval of natural skin component (e.g. lipids), prolonged exposure to water(e.g. long-term immersion in full-baths), a (repeated) disruption of thephysiological skin surface pH and excessive and/or prolonged occlusion of theskin should be avoided. However, the epidermal acidification is known to befragile and it is commonly accepted that cosmetic products, especially soapsand skin cleansing products, can induce significant changes in skin surface pH.The skin pH recovery needs time up to several hours before it can reach thephysiological level. Skin care delivered to improve, e.g. the outcome of an eczematherapy or to reduce, e.g. the adverse effects of a cancer therapy are oftentermed as adjuvant skin care. Nonetheless, adjuvant or the above describedclassic preventive skin care pursues the similar goals. Moisturizing preventsand alleviates skin irritation, soothing the skin by slowing the evaporation ofwater. Many liquid face cleansers also moisturize, which may be all that isneeded for a patient with oily skin. Protection from sun and environmentaldamage is important for all patients. While sunscreens are often irritants, thebest options for young, oily, acne-prone skin tend to have a water or lightliquid base. Moisturizing sunscreens are appropriate for patients with dry,sun-damaged skin, as well as those who wear makeup, have other skin diseases,or are easily irritated by products [3-6]. TYPES OF SKIN CREAMS They aredivided into two types: oil-in-water (O/W) creams which are composed of smalldroplets of oil dispersed in a continuous phase, and water-in-oil (W/O) creamswhich are composed of small droplets of water dispersed in a continuous oilyphase. Whether the aqueous or the oil phase becomes the dispersed phase dependsprimarily on the emulsifying agent used and the relative amounts of the twoliquid phases. Hence, an emulsion in which the oil is dispersed as dropletsthroughout the aqueous phase is termed an oil-in-water (O/W) emulsion. Whenwater is the dispersed phase and oil as the dispersion medium, the emulsion isof the water-in-oil (W/O) type. Oil-in-water creams are more comfortable andcosmetically acceptable as they are less greasy and more easily washed offusing water. Water-in-oil creams are more difficult to handle but many drugswhich are incorporated into creams are hydrophobic and will be released morereadily from a water-in-oil cream than an oil-in-water cream. Water-in-oilcreams are also more moisturizing as they provide an oily barrier which reduceswater loss from the stratum corneum, the outermost layer of the skin. It is important for pharmacists to know thetype of emulsion they have prepared or are dealing with, because this canaffect its properties and performance. Unfortunately, the several methodsavailable can give incorrect results, so the type of emulsion determined by onemethod should always be confirmed by means of a second method [7,8]. (Table 1). Cleansing creams In earliest times, cleansing wasdone by using a piece of bone or stone to scrape the skin. Later civilizationsused materials of plant origin along with water for cleansing. Many differentcivilizations can be given credit for discovering soap. The earliest mention ofthe soap making process can be found in Sumerian clay tablets dating to ca.2000 BC. By 600 BC, tree ash and animal fat had been used by the Phoenicians toprepare soap. The first cosmetic cleansing cream to be manufactured on anindustrial scale was cold cream, an emulsion made with mineral or almond oil alongwith beeswax, borax and water. A second type of cleanser was introduced around1920. It was made solely from oils and waxes, so was water-free (anhydrous) andwas not an emulsion. Cleansers of this type were designed to melt or liquefywhen applied to the skin – they were thixotropic – which is why they werereferred to as liquefying cleansing creams. Skin permeability was found todepend very strongly on temperature and less strongly on the duration ofheating. The pores of the skin are like little thermostats; they expand withheat and contract with cold. Now when a cream containing a high percentage ofwater is applied to the skin it is obvious that the pores will at once contractand prevent the deep penetration which is essential if the skin is to bethoroughly cleansed. Some chemists who favor cold cream type cleansers arguethat such a reaction is momentary and that with continued rubbing the skinwarms up and the pores open again. But they overlook the simple fact that waterbegins to evaporate immediately upon exposure and in evaporating it abstractsheat from the skin, which causes the pores to contractagain. Many of the environmental impurities and cosmetic products are not watersoluble and so washing the skin with simple water would not be sufficient toremove them. Substances capable of emulsifying them into finer particles are tobe used for making these fat-soluble impurities water soluble. Herein,cleansers fit into the picture. Skin cleansers are surface—active substances(i.e., emulsifiers/detergents/surfactants/soaps) that lower the surface tensionon the skin and remove dirt, sebum, oil from cosmetic products, microorganismsand exfoliated corneum cells in anemulsified form. Careful face washing helps to improve and prevent acne; however, intensive washing has a risk of inducing skin barrierimpairment and dry skin, especially in sensitive skin. An ideal cleanser shoulddo all these without damaging or irritating the skin, on the contrary it shouldtry to keep the skin surface moist. With the advent of advanced technologies,newer cleansers are now being manufactured which are mild, provide moisturizingbenefits and can be easily washed off. The combined use of a facial skincleanser and moisturizers is safe and effective for the care of acne inpost-adolescent women with sensitive skin. The key ingredients in cleansingcreams, which are also known as cold creams, are usually petrolatum, mineraloil, waxes and water. Many cleansing creams also contain emulsifiers, whichprevent the ingredients of the cream from separating into layers. It canmoisturize skin and remove dirt, sweat, make-up at the same time. The layers ofmake-up, dust and sweat remain as a layer on the face and prevent the skin frombreathing this may eventually lead to wrinkles and dullness. With their mildand effective action, cleansing creams now days have become a beneficialapproach to healthy skin care (Table 2)[10-16]. There is strong evidence that mineral oilhydrocarbons are the greatest contaminant of the human body, amounting toapproximately 1 g per person. Possible routes of contamination include airinhalation, food intake and dermal absorption. The present study aims toidentify the most relevant sources of mineral oil contamination [20].Petrolatum is thought to be occlusive, thereby blocking transcutaneous waterloss and trapping water under the skin's surface [21]. Petrolatum is a commonmoisturizer (Discussed in detail in often used in the prevention of skininfections after ambulatory surgeries and as a maintenance therapy of atopicdermatitis (AD) [22]. Common ingredients in emollients include petroleumproducts, glycerin, fatty acids and plant oils. An ideal emollient shouldcontain a combination of occlusive agents to slow down water loss, humectants toincrease capacity to withhold moisture and lubricants to reduce frictionagainst skin [25]. The exotic fats used in skin care are known to exhibit theireffects through restoration of a sufficient layer of skin lipids and skinelasticity, boost natural skin regeneration and increased skin hydration byforming an inert, epicutaneous occlusive membrane. Besides these facts, mangobutter which is one of several exotic fats is viewed as an ingeniousreplacement for cocoa butter, mineral and petroleum-based emollients because ofits appreciable contents which are very important as source of skin activeingredients [26]. Isopropyl myristate is a non-greasy emollient that isabsorbed readily by the skin. It is used as a component of semisolid bases andas a solvent for many substances applied topically [18]. IPM, the isopropylester of myristic acid, is used in cosmetics as a substitute for natural oilsbecause it has excellent spreading properties and is absorbed easily into theskin. In many topical and transdermal preparations, IPM is also used as aco-solvent with skin penetration enhancement properties of active ingredients[27]. Polysorbate20 is a non-ionic surfactant and emulsifier derived fromsorbitan monolaurate, and is distinguished from the other members in thepolysorbate range by the length of the polyoxyethylene chain and the fatty acidester moiety. Due to non-toxic nature, it is used as a wetting agent inflavored mouth drops such as Ice Drops, helping to provide a spreading feelingto other ingredients like SD alcohol and mint flavor [29,30]. Glycerin iswidely used in cosmetics and well as in pharmaceutical formulations, mainly ashumectant. In vitro studies haveshown glycerin to prevent crystallization of stratum corneum model lipidmixture at low room humidity (Figure 3).Ten days treatment of normal skin with 20% glycerin significantly increasedskin corneometer values, indicating an increased hydration [31]. A humectant attracts and retains the moisturein the air nearby via absorption, drawing the water vapor into or beneath theorganism's or object's surface. Muchmore is now known about the epidermis, and in particular, the stratum corneum.The “bricks and mortar” model suggests that its role is as an active membrane.Loss of intercellular lipids, i.e., the ceramides, cholesterol and fatty acidsthat form the bilayers, damages the water-barrier function. The stratum corneumthen calls into action repair mechanisms. Scientifically, the moisturizingtreatment involves a 4-step process: (a) Repairing the skin barrier (b)Increasing water content (c) Reducing TEWL (d) Restoring the lipid barriers’ability to attract, hold and redistribute water. The intended application of detergents andcleaners should not result in direct contact with product ingredients; however,misuse of the product could potentially cause dermal (skin and ocular) orinhalation exposure. Sodium Lauryl Sulfate (SLS) enters and maintains residuallevels in the heart, the liver, the lungs and the brain from skin contact. SLSis cited as causing severe eye damage and blindness. A second erroneous ocularhealth claim made about SLS is its link to cataract formation [32,34]. Forcleaning and industrial uses, it is monitored by the Environmental ProtectionAgency (EPA). Sodium cocosulfate, made from coconut oil, can be used as areplacement for SLS in your beauty product recipes [35]. Recent studies suggestthat coconut oil can be a useful surfactant when combined with Yucca schidigera extract [36]. Thepolysorbates are amphipathic, nonionic surfactants composed of fatty acidesters of polyoxyethylene sorbitan being polyoxyethylene sorbitan monolauratefor polysorbate 20 and polyoxyethylene sorbitan monooleate for polysorbate 80.The polysorbates used in the formulation of biopharmaceuticals aremixtures of different fatty acid esters with the monolaurate fraction ofpolysorbate 20 making up only 40-60% of the mixture and the monooleate fractionof polysorbate 80 making up >58% of the mixture [37]. The CosmeticIngredient Review (CIR) Expert Panel assessed the safety of 39 polyetherlanolin ingredients as used in cosmetics. The Panel concluded that thesepolyether lanolin ingredients are safe in the practices of use andconcentration as given in this safety assessment [38]. Nasrollahi et al. [39]revealed that Linoleic acid (LA) containing w/o emulsion exhibitederythema-reducing effects [39]. Sodium cocoyl isethionate (SCI) is an importantsurfactant ingredient in mild, syndet (synthetic detergent) cleansing bars. In vitro and in vivo studies have demonstrated that SCI is mild and lessdamaging to the skin barrier than soaps and surfactants such as sodium dodecyl sulfate (SDS) [40]. The CosmeticIngredient Review Expert Panel assessed the safety of triethanolamine (TEA) and31 related TEA-containing ingredients as used in cosmetics. The TEA is reportedto function as a surfactant or pH adjuster; the related TEA-containing ingredientsincluded in this safety assessment are reported to function as surfactants andhair- or skin-conditioning agents. The exception is TEA-sorbate, which isreported to function as a preservative. The panel concluded that TEA andrelated TEA-containing ingredients named in this report are safe as used whenformulated to be nonirritating. These ingredients should not be used incosmetic products in which N-nitroso compounds can be formed [41]. A cleansingcream or lotion is spread onto the skin, using the fingertips, and massagedonto the surface. This action serves to loosen and suspend the grime and soilin the emulsion. A subsequent wipe with a tissue or cotton wool pad removes themajority of the applied cleansing emulsion and with it the skin soil, grime ormakeup. The cream should have a medium-to-high percentage oil phase and beeasily spreadable, should not “rub in” and should not irritate the skin. Inaddition, if it can leave a residual emollient film on the skin, so much thebetter [99]. Surfactants in skin cleansers interact with the skin in severalmanners. In addition to the desired benefit of providing skin hygiene,surfactants also extract skin components during cleansing and remain in the SCafter rinsing. These side effects disrupt SC structure and degrade its barrierproperties. Hydrophobically modified polymers (HMPs) havebeen introduced to create skin compatible cleansing systems. At the presence ofHMP, surfactants assemble into larger, more stable structures. These structuresare less likely to penetrate the skin, thereby resulting in less aggressivecleansers and the integrity of the skin barrier is maintained. By creatingthese large polymer/surfactant complexes, the cleanser becomes less aggressive.In these HMP/surfactant systems, because less surfactant enters the SC, thereis less inflammation and therefore the skin barrier is less disturbed [146] (Figure 4). The legendary Roman Holiday actress oncefamously said, “I owe 50% of my beauty to my mother and the other 50% to ErnoLaszlo.” Erno Laszlo, a pioneer in 20th Century skin care, believedbeautiful skin was no miracle. He analyzed women's (and men's) skin giving themprecise techniques for their personal cleansing and prescribed the exactproducts for their particular skin type and concern. The backbone of anycosmeceutical skin care regimen is facial cleansing and moisturizing.Moisturizers create the illusion of smooth, soft skin by placing a temporaryfilm over the skin surface or by imparting a transient hydration benefit thatdoes not clinically improve the quality or appearance of skin. Cleansing,aggressive exfoliation and sebum reductionin the absence of a traditional moisturizer safely and effectively improvedmultiple clinical endpoints of photo aged skin. Cold cream The inventionof cold cream is credited to Galen, a physician in the second century fromGreece. This cold cream is thick and softens when it touches the skin. It isperfect for dry skin on elbow, feet and knees and also perfect for natural waysof removing makeup and to avoid eczema in dry parts of your body. Thecombination of fats and water in this product help moisturize – the cream getsits name because it's cold to the touch – with people using it to soften theirskin, soothe sunburns and protect faces from wintry weather, too. The emulsionis of a “water in oil” type unlike the “oil in water” type emulsion ofvanishing cream, so-called because it seems to disappear when applied on skin.Lubricating creams, night creams or massage creams are a type of cold creamwith the addition of lanolin (wool fat) and its derivatives. The name “coldcream” derives from the cooling feeling that the cream leaves on the skin. Coldcreams were usually made as water-in-oil (W/O) emulsions. After the creams areapplied to the skin much of the water evaporates leaving the remaining oil toact as a solvent which cleanses the skin of cosmetics and other grime. Theremay also be some surfactant activity. Some chemists suggested that as the waterevaporated it cooled the skin which is why the creams are called ‘cold cream’.An alternative explanation is that in the days before mineral oil or petrolatumwas used, the creams needed to be stored in a cool place to stop them goingrancid. This made them cold to the touch and so gave them their name. The firstcold cream has been attributed to the Roman physician Galen (C.E. 150) whoreputedly made a primitive emulsion by mixing water with molten beeswax andolive oil. It was laborious to make – requiring a great deal of mixing – andtended to separate on standing. However, the formulation persisted – generallyusing rose-water and/or oil of roses as a perfume – and was included in thefirst edition of the ‘Pharmacopœa Londinensis’ in 1618. Vegetable oils likealmond oil are liable to deteriorate when they are mixed with water, so earlyforms were not long-lasting. Their short shelf life meant that cold creams wereusually made up at home or purchased in small quantities, freshly made up by alocal pharmacist, chemist or druggist. Borax-beeswax cold creams were white;opaque had a high luster and spread easily on the skin, but the use of almondoil still limited the shelf life of the cream. When borax-beeswax cold creamswere made with petrolatum and mineral oil rather than almond oil, cold creamswere produced that were stable, cheap to produce and had a long shelf life.This made borax-beeswax cold creams ideal preparations for industrial manufactureand distribution. Cold creams that contained a high percentage of mineral oil(liquid paraffin) or petrolatum were regarded primarily as cleansers, to bespread on thickly, then removed with a cloth or tissues. However, depending onthe formulation, they could be used for a variety of purposes and were oftenadvertised as beauty creams or night creams. City air in most large westerncities was a good deal grimier than it is today. Dust, soot and otherparticulate matter collected on the face, making it an enduring problem. Earlyadvertisements for cold cream stressed the need to “cleanse your skin of allthe dirt which lodges in the pores through the day, and which, more thananything else, injures the skin”. It was also suggested that the cream be usedat night to give it additional time to act. Cold creams were widely used in thetheatrical trades to remove greasepaint with a number of suppliers producingproducts labeled as Theatrical Cold Cream. As the use of street make-upincreased, cold creams were also promoted as a way to remove face powder,lipstick, rouge, foundation and other forms of personal make-up. Cold creamsformed the basis of early beauty regimes developed by Pond’s, Elizabeth Arden,Helena Rubinstein and others. By establishing a daily regime, cosmeticcompanies hoped they would increase the usage of their creams and widenconsumer consumption to entire product lines. Guidance from beauty authoritiessaw many women adopt the practice of applying cold cream before sleep to removethe dirt, grime and cosmetics of the day. It cleansed the skin and, if notremoved with soap and water, left a thin film with moisturizing properties. Ifit was doing something else while you slept, so much the better. One wonders,for example, how many women discovered that leaving it liberally on their facewhen they retired, helped them avoid the ‘ministrations’ of their husbands,enabling them to get a night of uninterrupted sleep. The all-purpose nature ofcold cream, which had been its strength, proved to be its weakness. Therecognition of different skin types and skin conditions along with theproliferation of skin creams containing ‘beneficial additives’ saw the need foran all-purpose skin cream decline. This fracturing of the commercial skin-caremarket which began with the introduction of stearate (vanishing) creams in1892, picked up pace in the 1920s and 1930s and eroded the prestige of coldcreams and pushed them increasingly into the low-end of the skin-care market.Although the use of cold creams has declined, they are still available.However, when more recent products are compared to original formulations markeddifferences are evident, primarily in the replacement of borax with modernsurfactants (Figure 5) [42-50]. Cold cream isan emulsion of water and certain fats, usually including beeswax and variousscent agents, designed to smooth skin and remove makeup. Beeswax itself suffersfrom 2 disadvantages as an ingredient in skin creams. The first of this is thatit has a distinctive smell which usually has to be masked in the final product;the odor is not unpleasant but not found that compatible with the products ofmodern days’ sophisticated image. And the quality and price also vary with season.The original cold cream recipe or the basic cold cream formula contains Borax.Borax was added to the basic combination of ingredients at the end of thenineteenth century. It reacts with fatty acids in the beeswax to form anemulsion and makes the cream stable. Borax plays many different roles in coldcreams in that; it promotes emulsification and reduces surface tension ofwater. Borax is used in various household laundry and cleaning products but toits highly alkaline nature, it might cause skin irritation. There are alsoreports of adverse reproductive and developmental impact on the fetus. Its usein the long term is not recommended as there is a possibility of causing renaldysfunction as the borax accumulates in the body. It can also cause fatigue or vomiting due to toxicity.Some research suggests it could also cause genetic damage and be toxic tolymphocytes, the building block of the body’s immune system (Figure 6) [51-56]. Since borax is a naturally occurring mineraland is so useful in producing skincare and cleaning products, it is somewhatpuzzling why there is so much fuss about its use. It’s important to rememberthat “natural” doesn’t always equal safe, nor does it guarantee we areprotected from adverse effects. Sodium Behenoyl Lactylate can be used as anemulsifying agent, humectant and conditioner in skin and hair care. SodiumBehenoyl Lactylate is vegetable derived and can be used in creams, lotions,facial cleansers and bath products such as bath butters and scrubs [59,60].White beeswax is a chemically bleached form of yellow wax and is used insimilar applications: for example, to increase the consistency of creams andointments and to stabilize water-in-oil emulsions. White wax is used to polishsugar-coated tablets and to adjust the melting point of suppositories. Beeswaxhas been used since ancient times for its antimicrobial properties in Europeanand Asian traditional medicines. Preservative effects are possibly at the basisof its use in embalming and mummification practices by old Egyptians andPersian, or to model death masks by ancient Romans. A total of about 50 aromacomponents have also been reported. The ester/acid ratio is important forbeeswax characterization by different Pharmacopeias, being generally lower (3-4)in European and higher (8-9) in Asian beeswax [61,62]. Ceresin is often used asa substitute for ozokerite wax due to its similar properties, and also as asubstitute for beeswax and paraffin wax. It acts as a rheological modifier atlow concentrations (2-3%) and has the ability to create very smallcrystallites, which crosslink and establish a network structure that does notallow flow in practical conditions. Ceresin produces stable mixtures with oilsand prevents bleeding or sweating of oil and it produces a lighter cream thatis less greasy [18,63]. Carbopol® 934 polymer is a white powder,cross-linked polyacrylic acid polymer. It exhibits short flow properties and acreamy sensory profile, and is therefore well suited for use as a rheologymodifier in lotions and creams [64]. Butylene glycol is an antimicrobialpreservative; humectant; solvent; water-miscible co-solvent. It is used intopical ointments, creams and lotions and it is also used as a vehicle intransdermal patches. Cottage cheese whey was unsatisfactory, but B. polymyxaproduced large amounts of the glycol in sweet whey, about 60 mmol of glycol per100 mmol of lactose utilized [18,65]. It is widely used in cosmetics, includinglow-irritant skin care products and topical medicaments, as an excellent andlow-irritation humectant [66]. Polyethylene glycols (PEGs) are products ofcondensed ethylene oxide and water that can have various derivatives and functions.PEG-100 STEARATE (a polyethylene glycol ester of stearic acid, commerciallyavailable as HallStar® PEG 4400 MS; Jeemate 4400 DPS; Sabowax SE100) is a non-ionic emulsifier (o/w) from petrochemical and vegetal sources.PEG-100 stearate is off-white, solid ester of polyethylene glycol (a binder anda softener) and stearic acid. The surfactant qualities of glyceryl stearate andPEG-100 stearate allow oil and water to mix. Used in after sun skin care,antiperspirants, beach wear sun care, cleansing wipes. When it comes toevaluating skin care chemicals to find the best ingredients for skin care, PEG100 Stearate can be one of those cases where it’s difficult to make a clear-cutassessment. On the one hand, this ingredient has many positive properties, suchas the ability to moisturize and cleanse the skin. However, some studies pointto a potential link between PEG 100 Stearate and development of toxicity withinthe body. Some skin care experts even suggest that this ingredient has beenlinked to problems with reproductive health and even cancer. When looking atPEG 100 Stearate as an emollient, there are other ingredients, like shea andcocoa butter that can also do the job very well. Glycerin is another well-knownemollient that can increase skin hydration and softness. When it comes toemulsification properties of PEG 100 Stearate, alternative chemicals that aresometimes used include ceteareth 20, glycol stearate or laureth 3 [67-70].Sorbitol-based emulsifiers such as sorbitan sesquioleate (SSO) is used in avariety of products including skin care products, skin cleansing products,moisturizers, eye makeup and other makeup, primarily as an emollient. It isadded to formulas as a skin soother and moisturizer and is derived fromsorbitol, a humectant. They are commonly used in topical corticosteroids,topical antibiotics, topical antifungals, moisturizing creams and lotions andtopical retinoids. Contact dermatitis from sorbitol derivatives appears to beincreasingly prevalent. Patch-testing with SSO can be useful in the work-up ofpatients with presumptive cosmetic allergic contact dermatitis. Thosesensitized to SSO can be counseled to avoid sorbitol-containing products,especially topical corticosteroids [71-73]. Glyceryl Stearate acts asemollient; emulsifying agent; solubilizing agent; stabilizing agent;sustained-release agent; tablet and capsule lubricant. As a lubricant on theskin's surface, it gives the skin a soft and smooth appearance. It also slowsthe loss of water from the skin by forming a barrier on the skin's surface.Glyceryl Stearate and Glyceryl Stearate SE help to form emulsions byreducing the surface tension of the substances to be emulsified. In cosmeticsand personal care products, Glyceryl Stearate is widely used and can be foundin lotions, creams, powders, skin cleansing products, makeup bases andfoundations, mascara, eye shadow, eyeliner, hair conditioners and rinses andsuntan and sunscreen products [18,74,75]. Cetyl Alcohol is a synthetic, solid,fatty alcohol and nonionic surfactant. Cetyl alcohol is used as an emulsifyingagent in pharmaceutical preparations. Often confused with the bad alcohols,such as denatured alcohol, the fatty alcohols include, among others, cetylalcohol and stearyl alcohol. Typically, fatty alcohols are used as emollientsand thickeners in skin-care products. Fatty alcohols are not irritating and, infact, can be beneficial for dry skin [76-80]. Dimethicone is an antifoamingagent; emollient; water-repelling agent. Dimethicones of various viscositiesare widely used in cosmetic and pharmaceutical formulations. In topicaloil-in-water emulsions dimethicone is added to the oil phase as an antifoamingagent. It is hydrophobic and is also widely used in topical barrierpreparations. Also called polydimethylsiloxane, is a type of silicone oil withdistinctive properties that make it a useful ingredient in many skin careproducts. The combination of silicone with methyl groups tends to make itextremely resistant to water yet it keeps them flexible and movingfree, ideal properties for a lubricant. Dimethicone is viscoelastic meaningthat, at high temperature, acts like a viscous liquid and, at low temperature,acts like elastic solid, similar to rubber. According to USFDA, dimethicone atconcentrations between 1 and 30% is considered as a safe skin protectant.Besides being water and UV resistant, dimethicone is not greasy and is notexpensive [82]. Glydant Plus™ is a unique and cost-effective preservativefeaturing a high level of antimicrobial activity in a wide variety of cosmeticand personal care formulations. Glydant Plus is also highly effective ininhibiting the growth of gram positive and gram-negative bacteria, yeasts andmolds without the need of additional auxiliary preservatives. Thiswater-soluble preservative has a low odor and is stable for extended periods oftime over wide pH and temperature ranges [83]. Alpha-hydroxy acids (AHA) suchas glycolic acid have been used extensively in cosmetic and dermatologicalformulas. In low concentration (2-5%) glycolic acid is believed to facilitateprogressive weakening of cohesion of the intercellular material of the stratumcorneum (SC), resulting in uniform exfoliation of its outermost layers (thestratum disjunctum) [84]. Exposure to UVB radiation induces inflammation andfree radical-mediated oxidative stress through reactive oxygen species (ROS)that play a crucial role in the induction of skin cancer. Clinically chronicphotoaging may result in fine wrinkles, texture abnormalities, pigmentdyschromias and actinic keratoses [151]. Glycolic acid (GA) chemical peels area popular treatment for photo-aged skin rejuvenation although retinaldehyde(RAL)-based cosmetic creams are potentially better tolerated than chemicalpeels [85]. Short-term topical application of glycolic acid in a cosmeticformulation increased the sensitivity of human skin to solar simulatedradiation (SSR), while a comparable treatment with salicylic acid did not [86].Glycolic acid also stimulates the growth of new skin. Although the exact mechanismof action of glycolic acid is still unknown, alpha-hydroxy acids decreasecorneocyte cohesion and it has been suggested that this occurs by interferencewith the formation of ionic bonds. They dissolve adhesions between cells in theupper layers of the skin, inducing shedding of dry scales from the skin’ssurface, commonly referred to as exfoliation [87]. AHAs have been used assuperficial peeling agents as well as to ameliorate the appearance of keratosesand acne in dermatology. However, caution should be exercised in relation tocertain adverse reactions among patients using products with AHAs, includingswelling, burning, and pruritus [88]. GA suppressed the mRNA expression levelsof NLRC4 and AIM2 among the inflammasome complexes. GA also blocked interleukin(IL)-1β by reducing the activity of caspase-1 in the NHEKs. Treatment with GA(2%) inhibited UVB-induced inflammation marker NLRC4 protein levels in mousedorsal skin. The photoprotective activity of GA was ascribed to the inhibitionof ROS formation and DNA damage, as well as a reduction in the activities ofinflammasome complexes and IL-1β. GA has anti-inflammatory and photoprotectiveeffects against UVB irradiation (Figure7). GA is potentially beneficial to the protection of human skin from UVdamage [89]. A natural tocopherol and one of the most potent antioxidant tocopherols.It exhibits antioxidant activity by virtue of the phenolic hydrogen on the2H-1-benzopyran-6-ol nucleus [90]. Stability of vitamin E depends on its form,dl-α-Toc acetate being the most stable. It protects the skin from variousdeleterious effects due to solar radiation by acting as a free-radicalscavenger. Experimental studies suggest that vitamin E has anti-tumorigenic andphotoprotective properties [91]. Although many cosmeceuticals contain vitaminsC and E, very few are actually effective in topical application because thestability is compromised as soon as the product is opened and exposed to airand light. However, when a stable formulation delivers a high concentration ofnon-esterified, optimal isomer of the antioxidant, vitamins C and E inhibit theacute UV damage as well as chronic UV photoaging and skin cancer [92]. Thesolubility of ascorbyl palmitate in alcohol permits it to be used in non-aqueousand aqueous systems and emulsions. It is an anti-mutagenic agent; antioxidant[93]. Ascorbic acid-6-palmitate reduced cellular levels of reactive oxygenspecies following ultraviolet B irradiation. Ascorbic acid-6-palmitate stronglypromoted ultraviolet-B-induced lipid peroxidation, c-Jun N-terminal kinaseactivation, and cytotoxicity, however. Despite its antioxidant properties,ascorbic acid-6-palmitate may intensify skin damage following physiologic dosesof ultraviolet radiation [94]. Vitamin C also improves the elasticity of theskin and reduces wrinkles by stimulating collagen synthesis. Since itsuppresses pigmentation and decomposes melanin, it is used as a skin-whiteningagent. However, applied ascorbic acid is extremely reactive and thereforeunstable in dispersions due to the fast oxidation and further irreversiblechemical transformation. Therefore, the use of less reactive derivatives likeascorbyl phosphate salts (pro-antioxidant) or lipophilic ascorbyl esters is anattempt to prolong their stability [95]. Ascorbyl palmitate widely used in cosmeticand pharmaceutical preparations. Light accelerated the degradation of ascorbylpalmitate. In contrast, sodium ascorbyl phosphate was stable in both types ofmicroemulsions. Sodium ascorbyl phosphate is shown to be convenient as anactive ingredient in topical preparations [96]. The most common AHAs incosmetic products are glycolic acid and lactic acid. Among others are citricacid, hydroxycaprylic acid and hydroxycapric acid [97]. Night creams Night and massage creams are designed to beleft on the skin for several hours or to remain mobile on the skin even aftervigorous rubbing [98]. Therefore, they are composed with a substantial oilphase which will spread easily without disappearing but also without rubbingoff on to clothing or bed linen in use. Such creams tend to behigh-oil-content, water-in-oil, soft solid or viscous liquid creams. Amoisturizing effect is resulted due to the formation of the occlusive layer onthe skin surface thereby reducing the rate of trans-epidermal water loss.Hence, the skin surface feels smooth by lubricating action and allowing any“saw tooth” cells in the outer layer of the stratum corneum to be smootheddown. The occlusive layer prevents epidermal moisture loss and also giveslubrication. Massage has a valuable part to play in skin care since it is wellknown that vigorous rubbing of the skin prevents dead surface cells and keepsepidermal blood supply in good condition. The term “moisturizing” has also beenapplied to water-in-oil creams of this type. The recent research has broadenedthe concept of moisturizing from the simple occlusive skin barrier principle.Many night moisturizing creams are comparatively light and easy to rub incompared with those of the overnight and massage types, although there stillremains a market for the heavier moisturizing creams [99]. Recently, day andnight creams containing Melatonin, vehiculated in lipospheres (Melatosphere™),have been developed (Nutriage day cream and Nutriage night cream; CantabriaLabs, Difa Cooper, Caronno Pertusella, VA, Italy). Melatonin is considered as astrong antioxidant molecule, and it is one of the most potent ·OH radicalscavenger in nature. The liposphere carrier system could further improve thepenetration of the Mel molecules through the skin layers. In women with skinaging, Melatonin-based creams improved significantly skin tonicity and skinhydration with a significant reduction in skin roughness, supporting the skinanti-aging effect of this molecule applied topically (Table 3) [100]. Deionized (DI) water is water that has beentreated to remove all ions – typically, that means the entire dissolved mineralsalts [111]. Glycerin is used as humectant/emollient. Dermosoft®GMCY (Glyceryl Caprylate) is a skin-conditioning agent - emollient; surfactant- emulsifying agent [112,113]. synergistic effects of isopropyl myristate andglyceryl monocaprylate (GEFA-C8) enhanced transdermal permeation of PTZ bydisrupting SC lipids [114]. There is a considerable interest in the developmentof preservative-free or self-preserving cosmetics. Lonicera caprifoleum and Lonicerajaponica in combination with glyceryl caprylate and/or levulinic acid,p-anisic acid and ethanol (5%) gave an important assistance in order to boostthe self-preserving system and to produce stable and safe cosmetic products[115]. Glyceryl Caprylate is a preferred ingredient in many natural careproducts (claimed safe for baby products). It is derived from plants, and avaluable resource because of its many properties. Glyceryl Caprylatemoisturizes and balances the pH of the skin. Its antimicrobial and antifungalproperties keep bacteria-causing germs at bay. It also contains a naturalpreservative that prevents mold from forming. It is very compatible with knownorganic ingredients but can also interact with extra iron [116]. It’smoisturizing and re-fatting properties assist with improving and maintainingthe moisture and balanced environment of the skin. It can also help to combatimpurities due to its strong activity against Propionibacterium acnes [117]. Xanthan gum (XG) is a complexexopolysaccharide produced by the plant-pathogenic bacterium Xanthomonas campestris pv. (Xanthomonasbacteria, a Gram-negative bacteria genus that exhibits several differentspecies) and is widely used as a thickener (gelling agent) or viscositymodifier [118]. It is also used as stabilizing agent; suspending agent;sustained-release agent [18]. The use of bioadhesive hydrogels for skin carepresents important advantages such as long residence times on the applicationsite and reduced product administration frequency. Hydrogel formulations showeda prevalently elastic rheological behavior. Complex viscosity of carbomerhomopolymer type C hydrogels was higher than that of the kappa carrageenanhydrogels. Formulations which combined carbomer homopolymer type C with xanthangum or with carbomer copolymer type B were the most promising for bioadhesiveskin products [119]. It has widely been used as an additive in variousindustrial and biomedical applications such as food and food packaging,cosmetics, water-based paints, toiletries, petroleum, oil-recovery,construction and building materials and drug delivery. Recently, it has showngreat potential in issue engineering applications and a variety of modificationmethods have been employed to modify xanthan gum as polysaccharide for thispurpose [120]. Biophilic™ H is a patented phospholipid-based O/W lamellaremulsifier designed to create elegant and very comfortable formulas. Its lamellarstructure has a particular affinity to the skin, resulting in a second skineffect for maximum biocompatibility and tolerance [121]. Hydrogenated Lecithinis the product of controlled hydrogenation of Lecithin. Bilayers of thesephospholipids in water may form liposomes, a spherical structure in which theacyl chains are inside and not exposed to the aqueous phase. Lecithin andHydrogenated Lecithin are used in a large number of cosmetic formulations asskin conditioning agents-miscellaneous and as surfactant-emulsifying agents.Hydrogenated Lecithin is also used as a suspending agent-non-surfactant. Basedon the available data, Lecithin and Hydrogenated Lecithin are safe as used inrinse-off cosmetic products; they may be safely used in leave-on products atconcentrations up to 15%, the highest concentration tested in clinicalirritation and sensitization studies; but the safety of use could not besubstantiated in cosmetic products likely to be inhaled. Because of thepossibility of formation of nitrosamines, these ingredients should not be usedin cosmetic products in which N-nitroso compounds may be formed [122].Functionally sunflower oil is a diluent; emollient; emulsifying agent; solvent;tablet binder. Skin care influences skin barrier function during the firstpostnatal weeks. Sunflower oil did not harm skin barrier function adaptation inhealthy term neonates during the first five weeks of life [123]. Natural oilsare applied topically as part of a traditional oil massage to neonates in manydeveloping countries. Topical application of linoleate-enriched oil such assunflower seed oil might enhance skin barrier function and improve outcome inneonates with compromised barrier function. Mustard oil, used routinely innewborn care throughout South Asia, has toxic effects on the epidermal barrierthat warrant further investigation [124,125]. Topical application of olive oilfor 4 weeks caused a significant reduction in stratum corneum integrity andinduced mild erythema in volunteers with and without a history of atopicdermatitis. Sunflower seed oil preserved stratum corneum integrity, did notcause erythema, and improved hydration in the same volunteers. In contrast tosunflower seed oil, topical treatment with olive oil significantly damages theskin barrier, and therefore has the potential to promote the development of,and exacerbate existing, atopic dermatitis [126]. Several studies have shownsignificant differences between the moisturizing effects and skin tolerances ofvirgin and refined vegetable oils when incorporated in cosmetic emulsions. Thephospholipid content of Hazelnut oil decreased from 286 ppm in virgin oil totraces in refined oil. Still, moisturizing effect obtained with the emulsioncontaining the enriched refined oil was shown to be the same as that obtainedwith the virgin oil emulsion [127]. Hazelnut oil contains 66-85% oleic acid,7-25% linoleic acid, 4-9% palmitic acid and 1-6% stearic acid. When used incosmetics and personal care products, hazelnut oil and Hydrogenated HazelnutOil function as skin-conditioning agents - emollient and skin-conditioningagents – occlusive. It's loaded with skin-nourishing vitamins and essentialfatty acids that help protect skin against sun damage, boost collagenproduction, and more. Hazelnut is non-greasy and is best used for those whohave oily skin but still want to enjoy the many benefits of carrier oils [128].Vitapherole E1000 (Tocopherol and Helianthusannuus Seed Oil combination); Vitapherole® is a line of IPnatural-source vitamin E or tocopherols including α-tocopherols, mixedtocopherols and acetates. They protect the skin from environmental stressorslike pollution and UV. Tocopherols also help tighten and firm the look of skinwhich makes vitamin E the perfect addition to any anti-aging formula [129].Shea butter is a vegetable fat obtained from the fruit of a tree native toAfrica, Butyrospermum parkii. Sheabutter is primarily composed of fatty acids such as stearic and oleic acids.This product can be used in formulations from 1% to 100%. It is a naturalemollient that will add moisture back into the skin while also reducingswelling. Shea tree is abundantly found in the wide belt of savannah includingWest African countries like Nigeria, and further east in Uganda. Nowadays, sheabutter, mainly the traditional one (called BIO-shea butter) interests cosmeticand pharmaceutical firms, contained nutritional elements like essential fattyacids (oleic and linoleic acids), minerals (calcium, iron, copper, magnesium,sodium, potassium and zinc), vitamins (A and E) and carotene, which wouldpresent them as available, cheap and accessible nutritive edible fats[130,131]. Whitessence ™ is a strong natural lightening agent extracted fromAsian nangka seeds. The specific proteins of Whitessence ™ inhibit the transferof melanin from melanocytes to keratinocytes. The decrease in the melaninquantity at the surface of the skin results in a clear and unified complexion[132,133]. Exo-T™, exopolysaccharide from Kopara (microorganisms mat) living inunique ecosystem in the rims of French Polynesian atolls, acts as ananti-wrinkle agent, anti-aging agent and regenerating/revitalizing(manufacturer’s claim) [134]. Also, Tyrostat™ 9 is claimed as a potent stronginhibitor of tyrosinase enzymatic activity, one of the main enzymes involved inthe pigmentation process [135]. Potassium sorbate is a potassium salt havingsorbate as the counter ion. Potassium Sorbate is a mild preservative being usedin cosmetic and skin care formulas as a paraben alternative to prevent orretard the growth of microorganisms and protect products from spoiling.Phenoxyethanol, citric acid, sodium benzoate, and potassium sorbate were verycommon in all the cosmetic product categories, found in a study where 2300products commercially available in Spain was collected and examined to identifythe frequency of a wide variety of preservatives in different productcategories (Figure 8 and Exhibit 1) [136]. According to the magazine Longevity, PrincessDiana was “scrupulous about using an SPF-8 sunblock.” While the AmericanAcademy of Dermatology recommends applying at least SPF 30, protection againstUV rays can prevent both sunburn and dangerous skin cancers. Massage creams A beauty massages cream that promotesresilience and firmness while helping prevent sagging and other signs of aging.The great interest in eternal youth has developed a large market for skin careproducts claiming anti-wrinkle effects. Facial massage is an extremely popularform of beauty treatment and is thought to rejuvenate the skin. It may refreshthe subjects by reducing their psychological distress and activating thesympathetic nervous system [152]. Performing short-term facial massage with aroller increases SkBF and long-term use improves the vascular dilatationresponse [150]. Facial beauty treatment generally consists of three steps:vigorous massaging of the face with creams, steaming (using a hot towel or asteaming gadget), and application of a face mask containing adsorbents andastringents. Combining massage with moisturizer application is a populartechnique in beauty spa sessions. The subjective positive psychological effectsof massage with moisturizer application in hand and face beauty treatment aredocumented by many people attending spa sessions. Interestingly, dailyperformance of massage after moisturizer application was not an effectiveexternal intervention for enhancing moisturizer efficacy [147]. The action ofrubbing a cream or emollient into the skin is a form of massage, and thissimple action will go a very long way towards the recovery of skin integrityand in the prevention of harm and infection [148]. Anecdotally, the addition ofaromatherapy oils to massage cream may have a positive effect on symptom reliefin people with cancer, although evidence is again lacking [149]. Although thereare several subjective benefits with facial beauty treatment, there may beimmediate side-effects, such as erythema and edema, as well as delayedproblems, such as dermatitis and acneiform eruption (follicular eruptions characterizedby papules and pustules resembling acne), in about one-third of patients [101].Gentle massage is often facilitated using a cream to reduce friction on theskin. However, there is also the possibility of massage causing harm - massageor rubbing of vulnerable skin may exert shear stresses which may themselvespotentially cause damage. In addition, it is also possible that the use of acream or emollient as part of the massage regimen may increase epidermalhydration and prevent dermal stripping and the subsequent exposure of fragiledermal tissue [102]. Cellulite has been treated with massage which decreasestissue edema but it is also likely to have its effects at the cellular level bystimulating fibroblast (and keratinocyte) activity while decreasing adipocyteactivity. In addition to massage, effective topical creams with a variety ofagents were used to ameliorate the condition [103]. Slimming Cream Containing3.5% Water-soluble caffeine and xanthenes appears to be effective for thetreatment of cellulitis without serious adverse effects. Moreover, massage isalso used to remove interstitial fluid and accelerate lymphatic drainage, whichleads to the reduction of cellulite [157]. Client-preferred massage creams areideal for all modalities and offer a unique combination of medium glide,friction, and typically absorb completely into the skin. Massage Warehousecarries a wide range of organic massage cream brands including TheraPro,Massage FX, Lotus Touch, Soothing Touch, Bon Vital and much more! [104].Massage therapy has been shown to have beneficial effects on varying conditionsincluding prenatal depression, preterm infants, full-term infants, autism, skinconditions, pain syndromes including arthritis and fibromyalgia, hypertension,autoimmune conditions including asthma and multiple sclerosis, immuneconditions including HIV and breast cancer and aging problems includingParkinson's and dementia [105]. Thai foot massage may be one of the alternativetherapies to improve balance performance for diabetic patients as a result ofincreasing range of motion (ROM) and sensation of thefoot [106]. Massage in infancy improves growth and post-massage sleep. However,only sesame oil showed significant benefit [107]. Swedish Massage Therapy (SMT)is a complementary treatment that is believed to provide relaxation andtherefore able to reduce blood pressure caused by stress [108]. Massage creamsand lotions are well-suited to deep tissue and other high-friction massages.They tend to provide medium glide, and while they can be nourishing to the skin, aretypically absorbed fairly slowly. Lotion and cream are often similar products,but tend to have a different consistency. Creams are generally quite a bitthicker, while lotions are more liquid. Lotions tend to give more bang forbuck, as they are more spreadable. Creams do better for topical treatments ontough areas of skin. Some creams and lotions, particularly water-based ones,can leave the skin feeling dried out. Creams generally come in jars or tubs whichdon’t fit into holsters, which can be a hassle during treatments. Creams andlotions are often cold when first applied to the skin and can be difficult toheat. Many are also scented, which will bother some clients (Table 4) [109]. Ethylhexyl palmitate is an ingredient that functions as an emollient, solvent,pigment wetting agent, and fragrance fixative in cosmetics and personal careproducts. As an emollient, ethyl hexyl palmitate helps to keep the skin moistand supple by reducing water loss from the epidermis (the outer layer of skin).Emollients also act as lubricants by reducing friction when anything rubsagainst the skin. Ethyl hexyl palmitate is considered to be a non-occlusiveemollient, which means it does not form a film on the surface of skin. It isoften used as an organic replacement to silicones in a cosmetic formulationbecause it provides a dry-slip, silky feel that is very similar to how asilicone would feel. While all skin types can benefit from emollients likeethyl hexyl palmitate, emollients are very beneficial for those who have dry,rough and/or flaky skin. Emollients can treat these symptoms, leaving the skinlooking and feeling soft and smooth. In addition, emollients can benefit thosethat suffer from conditions such as eczema, psoriasis, or other inflammatoryskin condition [159]. Instruments that have been used for assessing epidermalhydration are based on measurements of conductance, capacitance and impedanceof the skin. Most of the commercial moisturizer contains Aloe barbadensis (Aloe vera)as a moisturizing agent. Ingestion of Aloe preparations is associated withdiarrhea, hypokalemia, pseudomelanosis coli (a disorder of pigmentation of thewall of the colon), kidney failure, as well as phototoxicity and hypersensitivereactions [160]. However, there so many other herb’s extract/juices/oils likegrape seed, cucumber, basil, jojoba oil, almond oil, olive oil, etc., presentin the commercial moisturizer section claiming for restoring skin hydration andviscoelasticity [161]. Many of grape seed oil's beauty benefits may be due toits omega-6 fatty acid content and vitamin E, an antioxidant that helps tobuild tissue and lineolic acid, a fatty acid which promotes hair and skin growth.Nonionic emulsifiers depend chiefly upon hydroxyl groups and ether linkages(from polyhydric alcohol anhydrides and polyoxyethylene chains) for theirhydrophobic effects [164]. Nonionic emulsifiers are usually less irritatingthan their ionic counterparts. Examples of nonionic emulsifiers includecholesterol, a natural component of the lipid bilayer, polyethylene glycol,cetearyl alcohol, ceteareth-20 and stearyl alcohol [162]. This non-ionicemulsifier blend, INCI Cetearyl Alcohol and Ceteareth 20, is a waxy pastilleand creates a thicker, waxier end product. It is derived from coconut fattyacid. It is excellent for foot and elbow creams, which are slightly heavier.Provides good emollience and feel. It forms highly stable emulsions withexcellent appearance and feel, compatible with a wide range of ingredients andpH [163]. Chemically, caprylic/capric triglyceride contains a highconcentration of fatty acids, which allows it to provide an occlusive layer tohelp increase moisture-retention at the skin's surface. As a result,caprylic/capric triglyceride can have emollient properties that may boostskin-hydration levels [166]. Application of the o/w emulsion formulationcontaining either HP or capric/caprylic triglyceride significantly elevatedskin moisture content and thus reduced transepidermalwater loss (TEWL) by a maximal approximately 33% against the controlformulation within 3 h and maintained this up to 6 h [167]. Germaben II-E canbe used in problem formulations, without the need for additionalco-preservatives. It is compatible with almost all cosmetic ingredients,including surfactants and proteins. Germaben II-E is a clear viscous liquidpreservative system with a characteristic mild odor. It is readily soluble at alevel of 1.0% in both water/oil and oil/water emulsions, but not in wateralone. Germaben II contains propylene glycol, propylparaben, methylparaben anddiazolidinyl urea. Some studies have raised concerns that paraben substancesmay be carcinogenic owing to their effect of mimicking the body’s hormoneestrogen” [168-170]. VITAMINS USED IN SKIN CREAMS The number ofcosmetic products which include vitamins as a constituent has increasedthree-fold since 1991. Vitamins are commonly used as ingredients of productsdesigned to improve the appearance and health of the skin; for this reason, thecutaneous benefits of such products are actively researched by dermatologistsand chemists. It has been claimed that fat-soluble as well as water-solublevitamins are capable of being taken up through the skin. The use of stabilizedvitamins in cosmetic preparations for external application is justified [171].Pantothenic acid is a part of the water-soluble vitamin B complex. Itsprecursor and the related materials – panthenol, pantethine and pangamic acidhave all been quoted as having a beneficial action on the skin and being usefulin skin and/or hair preparations. Skin softening ability of pantothenicacid-based topical products has also been demonstrated in a few recent clinicaltrials [172]. Although there is no certain proof that they penetrate the skinand reach the location where they might exert an influence, vitamin B complex,panthenol and vitamin B6 (pyridoxine) are used in some cosmetics. Vitamin D,like vitamin A, is oil-soluble and is essential for skin health, butdeficiencies are best corrected by oral administration to achieve a systemiceffect. However, vitamins D2 and D3 (calciferol) are used, sometimes inconjunction with vitamin A. A mixture of vitamins A, E and D3 has been claimedto be synergistic. Vitamin E is said to enhance percutaneous resorption andvitamin H is claimed to help fat and cholesterol synthesis. Other vitaminshaving some using topical preparations include the so-called vitamin F, nowknown as essential (unsaturated) fatty acids (EFA) [173]. MOISTURIZER This term was developed by marketers, promotingits function to moisten the skin. Moisturizer and emollient are often regardedas synonymous, even when occlusive and humectants are also part of it.Emollients are mostly made up of lipids and their components, which fillintercorneocyte cluster gaps to enhance skin hydration, smoothness, softness,flexibility. Occlusive are other type of moisturizer which is mostly oil basedand serve the function of maintaining skin water content by creating ahydrophobic barrier over the skin and blocking trans-epidermal water loss. Thelast type of moisturizers are humectants that consist of hygroscopic substanceswhich help the stratum corneum to absorb water by attracting water from dermisand a humid environment into the epidermis. The efficacy of moisturizersdepends largely on proper selection and compliance to continuously use it[199]. Moisturizers, among all other skin creams, most widely used. If water islost more rapidly from stratum corneum than it is received from the lower layerof the epidermis. The skin becomes dehydrated and loses its flexibility. Wateralone will not restore the flexibility [174,175]. There are two basic types ofdry skin. The first is due to prolonged exposure to low humidity and airmovement. The second is due to ageing related physicochemical changes. Again,dry skin or xeroderma is an extremely common problem which can be induced bycomplex interactions between environmental and individual factors including,but not limited to: low environmental temperature, low humidity, exposure tochemicals, microorganisms, aging, psychological stress, atopic dermatitis andeczema. Eczema common among young children. Other conditions, such as psoriasisand type 2 diabetes, can also cause skin to dry out [32,184]. Xerosis isabnormal dryness of the skin (Figure 9),mucous membranes, or conjunctiva (xerophthalmia). There are many causes ofxerosis and treatment depends on the particular cause [198]. Dry skinconditions are often not considered important by health professionals, and as aconsequence treatment are frequently under-prescribed. As a result of this,problems with untreated dry skin can lead to a variety of issues. Conditionssuch as pruritus and ichthyosis vulgaris can be distressing, while ezcema andpsoriasis can lead to more serious consequences such as fissures and infectionsand can result in a reduced quality of life and social isolation [200].Moisturizers are topical products designed to improve and maintain the skinbarrier function and to help prevent dry skin. It is common to think that amoisturizer adds water to the skin; however, this is a misunderstanding.Rather, a moisturizer works by preventing or reducing water evaporation fromthe skin [8]. This action allows the skin to rehydrate from within. There arethree classes of chemical ingredients that regularly serve as moisturizers: occlusive,humectants and emollients. Often these chemicals are either the same as orsimilar to natural components in the SC. They are often used in combination,with some ingredientsproviding overlap of characteristics[176,177]. Normal skin contains lower levels ofhistamine and inflammatory cytokines compared to dry skin. Premature expressionof involucrin, a protein that forms a protective envelope around corneocytes,has been implicated in the pathophysiology of dry skin. In addition, xeroticskin has been shown to contain higher levels of keratin 5 and 14 and lowerlevels of keratin 1 and 10 compared to normal skin. The schematic on the rightshows the cracked stratum corneum that is characteristic of dry skin andassociated with decreased water content (blue spheres) and increased involucrincross-linking (yellow crosses). Occlusion (by lanolin, petroleum, silicones,mineral and vegetable oil) prevent water loss from healthy normal skin causingthe stratum corneum to be more hydrated, making it softer and supple. Examplesof occlusive are: mineral and vegetable oils, lanolin and silicones. Theireffect is increased by the use of mixtures of lipids and other fatty chemicalswhich have been designed to imitate the composition of the skin’s natural oilysecretions. More recently, skin substantive barrier materials (mainly based onquaternary ammonium complexes) have become available which seem to be able toinfluence the rate of trans-epidermal water loss without putting an inclusiveor greasy barrier on the skin surface. These materials can be shown to besubstantive to skin (and hair) and act not only as moisturizers, but asemollients and skin conditioning agents. Examples are quaternium, ahydroxyethyl-cellulose derivative [178]. Humectants (Glycerol, Ethylene Glycol,PG, sorbitol alone or in admixture at various levels) attract water fromatmosphere, so supplementing the skin water content. They can be used alone or ina mixture at various levels. Whether or not they penetrate the skin surface isa moot point, but at least they will attract moisture to the skin. [179,180].The third and most valuable approach to miniaturization to supplementing Natural Moisturizing Factors (NMF) from the skin thoseare removed by polar solvents and detergent solutions. The NMF contains acombination of several naturally occurring free amino acids, urocanic acid,inorganic salts, sugars, lactic acid and urea. Many of these are highly efficientat attracting and binding water from the atmosphere, allowing adequatehydration of corneocytes even in low humidity environment. Once applied to theskin, the ingredients can stay on the surface, be absorbed into the skin, be metabolizedor disappear from the surface by evaporation, sloughing off or by contact withother materials. In addition to substances considered as actives, e.g. fats andhumectants, moisturizers contain substances conventionally considered asexcipients (e.g. emulsifiers, antioxidants, preservatives). Partitioning ofantioxidants, hydrogen bonding, interphase transport, surface accessibility,and interaction of emulsifier with antioxidants are considered to be importantparameters that determine antioxidant activity in lipid-containing systems.Some formulations may deteriorate the skin condition, whereas others improvethe clinical appearance and skin barrier function. For example, emulsifiers mayweaken the barrier. On the other hand, petrolatum has an immediate barrier-repairingeffect in delipidized stratum corneum. Moreover, one ceramide-dominant lipid mixture improved atopic dermatitis and decreased TEWL in an open-label study in children[181-183]. A typical moisturizing formulation is detailed in Table 5. IsopropylLinoleate the ester of isopropyl alcohol, it is a pale yellow, oily liquid. Incosmetics and personal care products, Isopropyl Linoleate may be used in theformulation of face and skin care products, hair care products and eye andfacial makeup. It acts as a lubricant on the skin's surface, which gives the skina soft and smooth appearance [185]. The structure of a stable O/W cream ischaracterized by a more or less pronounced mixed crystal bilayer. The additionof co-emulsifiers in order to achieve a soft formulation often leads to a mixedcrystal bilayer network of high viscosity and even phases separation. In orderto avoid this component of different chemical identities are used which oftenare not inert or harmless if they are absorbed. The amount of co-emulsifierused should not be too high, as it would crystallize increasingly duringstorage which gives the preparation an optical inhomogenity and a lack insoftness which is needed for a suitable cosmetic acceptance. A slightly higherconcentration than is necessary for the mixed emulsifier system can be advantageous,as the formation of a separate crystalline lipophilic network in thepreparation increases its viscosity which will lead to a higherphysico-chemical stability of the formulation. These results were obtained withthe co-emulsifiers glyceryl monostearate (Imwitor 900), cetylstearyl alcohol(Lanette O) and PEG-20-glycerolstearate (Tagat S2) as O/W emulsifier [186].Glyceryl Monostearate Emollient; emulsifying agent; solubilizing agent;stabilizing agent [18]. Diisopropyl adipate (DIPA) is a fatty acid ester and anisopropyl ester; clear, colorless to light yellow viscous liquids. It is usedfor a variety of applications, such as the production of moisturizers, shavinglotions and cleaning agents. DIPA acts as a lubricant on the skin surface whichgives the skin a soft and smooth appearance. Its solvent properties allow itsuse as a carrier for other cosmetic ingredients and also to soften syntheticcompounds by reducing brittleness and cracking [187]. Myristyl Myristate is a100% natural vegetable derived ester utilizing only the Myristic fatty acids.Non-greasy solid emollient, enhances esthetic properties of skin care products,gives more body and spreadability, results in superior whitening to the productand improved benefits to the skin [188]. About PEG-40 STEARATE: PEG-40 stearateis a synthetic polymer composed of PEG (polyethylene glycol) and stearic acid,a naturally occurring fatty acid. Products and formulas containing PEG 40Stearate should not be used on broken or irritated skin. Although PEGs areconsidered safe for use topically on healthy skin, studies showed that patientssuffering from severe burns were treated with PEG-based antimicrobial cream;this treatment resulted in kidney toxicity. Due to the presence of PEG, thisingredient may contain potentially toxic manufacturing impurities such as1,4-dioxane [189]. Cetyl alcohol is a common choice of emollient. It forms alayer on the skin, which traps the water on the skin and prevents it fromescaping, thereby inhibiting skin dehydration [190]. Ceteareth-20 functions asan emollient and emulsifier. It's usually used in conjunction with otheralcohols and fatty acids, working to thicken a solution and help otheringredients dissolve in a solvent. It also functions as a nonionic stabilizerin oil in water emulsions. Ceteareth-20 is the polyethylene glycol ether ofcetearyl alcohol; may contain potentially toxic impurities such as 1,4-dioxane[191]. Quaternium-22 is a light amber-colored liquid, a quaternary ammoniumsalt. The unreacted monomer content of these ingredients was considered low andof no toxicological concern. Limited data showed no skinirritation/sensitization. Although these ingredients were non-genotoxic inbacterial assays, mammalian genotoxicity, carcinogenicity, and reproductive anddevelopmental toxicity data were not available [192]. However, its toxicity isdue to its ability to act as a nitrosating agent, releasing potentiallycarcinogenic nitrosamines [193]. Hydroxyethyl cellulose is a polysaccharidederivative with gel thickening, emulsifying, bubble-forming, water-retainingand stabilizing properties. It is used as a key ingredient in many householdcleaning products, lubricants and cosmetics due to its non-ionic andwater-soluble nature [194]. Propylene glycol is a synthetic liquid substancethat absorbs water. It is a clear, colorless, viscous, practically odorlessliquid, with a sweet, slightly acrid taste resembling that of glycerin. It is apropanediol that exists as a clear, colorless and hygroscopic liquid andconsists of propane where the hydrogen at positions 1 and 2 are substituted byhydroxyl groups. It acts as Antimicrobial preservative; disinfectant;humectant; plasticizer; solvent; stabilizing agent; water-miscible co-solvent.Propylene glycol is used as an organic solvent and diluent in pharmaceuticalsand many other industrial applications (Figure10) [195]. In the winter season when the air is crispand chilly, a special skin care is necessary. Dry skin in the winter has beenreported to involve scaling, defects in water holding and barrier functions anddecreased ceramide levels in the stratum corneum (SC). Indicators of dry skinconditions (conductance, dryness, roughness and scaliness) strongly correlatedwith the level of ceramide. Daily application of a moisturizing cream iseffective in improving mild subclinical inflammation that is induced on the facialskin by the winter environment (Exhibits2-4). VANISHINGAND FOUNDATION CREAM The majority of the products are moisturizerswith added ingredients to support marketing claims. Whether the product is afacial foundation, an anti-aging night cream, a sunscreen, a topicalantioxidant or a skin-lightening serum, the formulation is basically amoisturizer. Skin care products are numerous and perplexing, yet there iscertain commonality among 80% of the formulations [208]. In order to achieverapid ‘Rub in’ effect, vanishing creams are composed of emollient esters in oilphase which leave little apparent film over skin. For this reason, a lowpercentage oil phase usually chosen. The presence of the humectant glycerin wasalso used to claim that they helped reduce moisture loss from dry skin.Vanishing Cream is made especially for the outer skin. It is greaseless. Itcontains a marvelous substance that prevents loss of skin moisture – actuallyreplaces lost moisture [209]. Major difference with cold cream is that coldcream is an emulsion of water and certain fats, usually including beeswax andvarious scent agents, designed to smooth skin and remove makeup. The emulsionis of a “water in oil” type unlike the “oil in water” type emulsion ofvanishing cream, so-called because it seems to disappear when applied on skin[210]. The history of foundation use can be traced back as far as 200 B.C. Itwas considered fashionable to have a pale complexion, so Greek women appliedwhite lead powder and chalk to lighten their skin. Roman women and men alsolightened their skins using white lead, chalk, and tin oxide-based creams. Thisfashion continued during the middle ages up to the early 19th centurywhen consumers used numerous toxic concoctions to lighten their skin [217].Foundation creams possess many of the same properties of vanishing creams.Foundation creams process many of the same properties. These creams are fordaytime use to protect and “condition” the cleansed skin. It is important to knowwhether a foundation provides sun protection and whether it meets the standardsset for other sunscreen products. Sunscreen agents help to protect theconsumer’s skin from the harmful, aging effects of shortwave solar radiation.Foundation cream comes in several forms: the original cream, a lighter mousseversion, a heavier stick version and a “pancake” version, a powder that turnscreamy after spraying it with water. There's also a relatively new hybridcalled cream to powder foundation (also called dual-finish foundation), whichlooks like a powder and applies like a cream if it is wet and then dries to apowder finish. Protection which is imbalanced for either UV-B or UV-A radiationis potentially harmful for users believing themselves adequately protected.Foundations proved to be much more interesting because they possess anon-negligible SPF as well as good photostability making these products safe interms of their mode of application (applied once daily in a study) [214]. Theymust therefore leave the skin non-greasy and preferably matte so that othermakeup can easily be applied over it. Modern foundation creams are of excellentappearance and stability. They contain emollients and moisturizers. In terms ofspreadability, coverage and adhesion, the results of group who used the ‘oscillationapplicator’ were significantly twice as high as the other group who applied byhand [215]. The right foundation helps creating illusionof flawless skin. Foundation is arguably the most important part of our makeuproutine. It covers blemishes, evens out skin tone and mattifes or illuminatesdepending on needs (Figure 11) [221]. Clients with pigmented skinare often coerced into purchasing a foundation that has too much white pigment[216]. Pigmented foundation creams can contain from 3-25% of pigments. Thosewith between 3 and 10% form a suitable substrate for the use for the subsequentuse of powder, whereas those with higher pigment concentrations can be used ascomplete makeup and are often termed powder creams. They can bewater-continuous or oil-continuous systems in liquid or solid form. Thedifficulties encountered in the preparations are: (a) The preferentialabsorption of emulsifier in the high surface of the pigment may sometimes causeinversion of the emulsion; (b) The inadequate dispersion of the pigment forreproducible colors. Pigments can be suspended by the use of cellulosederivatives or inorganic silicates such as bentonite or hydrated magnesiumsilicate [99]. According to dermatologists, it has been researched that thefoundation cream covers the skin pores to produce a radiant look causing porecongestion and disrupt the skin from breathing. Not only that, after a longtime it has been observed that the cream becomes oily which might result intoblemishes and peeling especially dry skin. It is therefore advisable that afterusing foundation cream the layer should be thoroughly wash in the evening orelse face the consequences of inflammation, acnes, rashes and pimples as theskin might be stuck with this. Women with status cosmeticus cannot toleratemakeup and complain of a continuous burning sensation after any application (Table 6) [219]. HAND AND BODY CREAMS (ALL PURPOSE CREAMS) True to its name, all-purpose cream is aflexible and versatile type of cream that can be used for both your savory andsweet creations [207]. They act nourishing or night cream when appliedexcessively, they function as hand creams when applied sparingly, thus they arecalled all-purpose cream [220]. All-purpose creams are typified by a W/Oemulsion or by high oil content O/W emulsions. These products are for generalface and body usage and generally have a heavy consistency and significant dragon rub-out [42]. The cream is pourable at room temperature but can also beeasily wiped when chilled. Preparations should comply following requirements:(a) As a foundation cream for general use it must provide a satisfactoryfoundation base for make-up without being too greasy (b) As a cleansing creamit should liquefy quickly, be of an oily nature but should be free from ‘Drag’.It should not be readily absorbed by the skin (c) As a hand cream it should beemollient yet not leave a greasy or sticky film on the skin (d) As a protectiveand emollient cream, it should leave a continuous but non-occlusive oil film onthe skin. There appears to be a market for all purpose cream because: (i)Unsophisticated user who are unwilling to pay money therefore buys one cream todo as much as possible (ii) Slightly more sophisticated user who buys aspeciality cream for one particular function and uses it as a speciality cream(iii) User who finds the cream ideally suited to their particular skin (iv) Theuser who particularly fragments their skin creams but resorts to an all-purposecream when travelling or on holiday (v) For general family use and protectionagainst the elements [48]. EPILOGUE The skin plays many roles ranging from barrier function to highlycomplex biochemical and photobiochemical processes. If we follow thisdefinition then skin care products are inherently not simply cosmetics tobeautify the appearance of the skin. Many cosmetic formulations have complexmixtures of actives and the interactions of which are not all well-defined.They then affect either the structure or the function (or both) of the skin.Unlike drugs, cosmetics typically are very safe and have few significantserious adverse events. However, like drugs, these active agents can impactmany diverse functions of the skin and we do not fully comprehend theimplications of these actions in many cases. Skin care products are readilyavailable and their promotions with fanciful claims are omnipresent. Thepromotions are based on effects, evoked by actives that are delivered throughvehicles that rely on specific technologies. Due to the fact, that theseproducts are in direct contact to the target tissue, their vehicle andingredients are able to profoundly modulate the characteristics of the skin andsome of its functions. This makes products for the skin absolute unique andversatile delivery systems. Currently the majority of skin care products arecosmetics. In cosmetic products claims often describe their functionalities andmay be as simple as “soothe signs of dry skin” but may also be more fancifullike “Multi-ingredient anti-aging moisturizer designed to improve theappearance of facial skin”. Skin care products are characterized by effects,evoked by actives that are delivered through vehicles that rely on specifictechnologies. The regulatory situation is unknown to most of the consumers andhealthcare professionals. They have to trust the current regulations oncosmetic products and quality standards used by the manufacturer. This meansthat professional healthcare practitioners have a substantial responsibilityfor skin health while delivering skin care. ARTICLE SUMMARY Skin care provide almost any possible kind ofvehicles, including emulsifiers, surfactants, oils and butters, waxes, andhydrophilic solutions. These substances combine the properties of drug deliveryto the skin, typical of vehicles, with the ability to produce specific actionson the skin, such as occlusive, moisturizing, smoothing, firming, soothing andconditioning effects. This term “Cosmetics” indicates cosmetic-pharmaceuticalhybrids aimed at enhancing the beauty of the skin by means of ingredients thatmodify skin functionality or provide additional health-related function orbenefit. As well as giving beauty to a person via the skin, the cosmeticindustry has now strongly linked its products medicinally to the subject ofanti-ageing of the skin. The industry has also coined such terms as actives,cosmeceuticals, nutricosmetics, etc., and the legislation associated with cosmetologyand dermatology has become similar. ACKNOWLEDGEMENT It’s a great honor and gratitude to bepharmacists in research and education process. All pharmacists, officials,journalists, magazine analysts and associates that I met in this purpose, werevery kind and helpful. I’m thankful to Lauren Balukonis, account executivewithin the beauty division at 5W Public Relations, working with bothentrepreneurs and established brands. I’m also grateful to seminar library ofFaculty of Pharmacy, University of Dhaka and BANSDOC Library, Bangladesh forproviding me books, journal and newsletters. The greatest help was fromstudents and colleagues who continually supported me in collection and dataextraction from books, journals, newsletters and precious time in discussionfollowed by providing information on different types of cosmetics in use. Aportion of this article is long been lectured as course material. So, it isvery much helpful for me to deliver better than before as many more things arestudied. COMPLIANCE WITH THEETHICAL ISSUES Ethics approval and consent to participate Animal and Human experiment: N/A Human Data Submission Approval: N/A Consent forpublication Consent to publish Individual Person’s data: N/A Availability of dataand materials Data sharing: Please contact author for data requests. Competing interests The author declares that he has no competing interests. Funding Funding from individual/Organization: N/A Authors’contributions The individual contributions of authors: N/A
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