FIELD OF THE INVENTION

The present specification relates to topical skin care compositions comprising niacinamide, glycyrrhetinic acid, filagrinol and pseudo-ceramide. Methods of preparing such compositions are also provided.

BACKGROUND OF THE INVENTION

Atopic dermatitis (AD) is a chronic, relapsing, inflammatory skin disease that typically starts in early childhood and can persist into adulthood in some cases. The etiology of AD is not well understood. Evidence suggests that AD is a multifactorial disease with complex interplay between genetic and environmental factors. Studies using instrumental devices have revealed that the water content of the stratum corneum is decreased in patients with AD. In addition, atopic skin shows a defective barrier function, as measured by the transepidermal water loss (TEWL), in both involved and uninvolved skin. AD is characterized by highly pruritic outbreaks, xerosis, and cutaneous inflammation manifesting as acute, subacute, or chronic eczematous dermatitis. Clinical phenotypes include xerotic skin changes, eczematous plaques in various stages, lichenification, marked pruritus, associated sleep disturbance, increased Staphylococcus aureus colonization, and predisposition to skin infection, with laboratory assessments showing increased immunoglobulin E (IgE) and eosinophil counts in most cases.

Psoriasis in general is a skin disease involving acceleration of epidermal proliferation and proliferation of capillaries in the dermal region evidenced by the presence of skin elevations and scales, which may be silvery in appearance. In addition, psoriasis frequently results in the exfoliation of the dermis and epidermis by inflammation of the affected cells.

Cosmetic xerosis or dry skin is a condition in which there is a disruption of water ingredients within the stratum corneum. A change in the barrier homeostasis of the stratum corneum can occur for a variety of reasons including low environmental temperature and humidity (e.g. winter), abrupt changes in environmental conditions and soap induced dryness.

Pharmacotherapies, such as steroids, an ti -histamines, antibiotics are usually prescribed for atopic dermatitis. The steroid agent (adrenal cortical hormone agent) can act as an anti-inflammatory and immuno-suppressant and has positive effect in treating the disease, but if used over a long period of time, side effects such as skin-weakening, symptom of systemic hormone, toxicity can result. Currently, uses of immune-suppression agents and novel anti-histamine agents have been studied for treating atopic dermatitis. However, anti-histamine agents cannot completely suppress the allergic reaction since other chemical transmitters in addition to the histamine can induce the allergic reaction. The mast cell releases other chemical transmitters such as leukotriene C4 and leukotriene B4 in addition to the histamine. Leukotriene C4 contracts the smooth muscle of bronchus like the histamine, and leukotriene B4 causes chronic inflammation by inducing neutrophil and eosinophil and injures neighboring cells.

The psoriasis, dry skin conditions are most commonly treated with topically applied moisturizers. Moisturizer formulations are designed with specific ingredients including oils, emulsifiers and humectants that influence their aesthetic properties and can affect the function of the stratum corneum. However, frequent re application for maintaining the skin hydration, sticky nature, are most common drawbacks in conventional moisturizers.

Therefore, a novel skin care composition for the effective treatment of atopic dermatitis, psoriasis, dry skin without the side -effects is required.

Niacinamide or nicotinamide, also known as vitamin B3, is an essential dietary vitamin whose deficiency leads to pellagra. It is converted in vivo from nicotinic acid, which has the same vitamin activity as its amide. Niacinamide has been shown to promote increased differentiation and elevated synthesis of ceramides, free fatty acids and cholesterol in a cell culture model of human keratinocytes. Several prior arts have suggested that topical treatment with niacinamide may have some beneficial effects on certain skin conditions, such as acne vulgaris, photodamage, cutaneous hyperpigmentation. Topical application of niacinamide also increased ceramide and free fatty acid levels in the stratum corneum (SC), and decreased transepidermal water loss (TEWL) in dry skin. It exists either in the form of white crystalline powder or of colourless crystals. Niacinamide is a water-soluble vitamin having molar weight of 122.12 g/mol, with following structural formula:

A ceramide is a combination of a fatty acid and a sphingoid base, joined by an amide bond between the carboxyl group of the fatty acid and the amino group of the base. Ceramides are present in lipid lamellar phase of stratum corneum, the outermost layer of skin, is known to provide an epidermal barrier against trans-epidermal water loss as well as environmental irritants. It has been found that ceramides inhibit the action of certain substances, such as elastase and collagenase, which degrade collagen, elastin and other skin proteins that ensure that the cement that holds the horny cells remains in good condition. It plays critical role in both forming lipid bilayers and generating structural stability of resulting lamellar phase, which is closely related to the control over the mechanical properties, such as diffusivity and elasticity. The loss of ceramides from the skin causes dryness, peeling, cracking and itchiness. In nature, unfortunately, ceramides exist only in an extremely small quantity. Moreover, it is really difficult to extract them with high purity in large production scales, which hampers their wider use in industry. To make them commercially available, synthetic pseudo-ceramides (e.g. Hydroxypropyl Bispalmitamide MEA or Ceramide PC- 104) have been developed and used to reduce transdermal water loss, thus moisturizing the skin in dermato logical and cosmetic applications. Ceramides have following structural formula:

Filagrinol is an active composed by unsaponifiable fractions of olive, soybean, wheat germ oil and pollen extract. It is a clear yellow-amber liquid (T=20°C), with characteristic odour, soluble in lipid systems. It does not contain any preservative. Filagrinol stimulates filaggrin production, an essential protein synthesized in the Stratum Granulosum, that promotes organization and aggregation of keratin and enhances the NMF (Natural Moisturizing Factor), a pool of low-weight hydrophilic molecules which bind water, necessary for both skin hydration and integrity. It has been used in cosmetic products for the treatment of dehydrated, sensitive, dry and reddening skin.

Glycyrrhetinic acid or glycyrrhizin or enoxolone is a pentacyclic triterpenoid derivative of the beta-amyrin type obtained from the hydrolysis of glycyrrhizic acid, which is obtained from the herb liquorice (Glycyrrhiza glabra). It is used to enhance the appearance of dry or damaged skin by reducing flaking and restoring suppleness, skin conditioning, skin-softening and anti-irritant agent. Glycyrrhiza glabra has significant anti-inflammatory and anti-allergic activity and has been used in herbal medicine for skin eruptions, including dermatitis, eczema, pruritus and cysts. Glycyrrhizin reinforces Cortisol's inhibition of antibody formation, stress reaction, and inflammation. It has following structural formula:

In an attempt to develop a novel skin care composition effective for the treatment of atopic dermatitis, psoriasis, dry skin or other skin related disorders, the present inventors have surprisingly found that use of niacinamide, glycyrrhetinic acid, filagrinol, pseudoceramide and one or more pharmaceutically accepted excipients resulted in compositions, which are stable, having efficient moisturizing effects, does not have unwanted side effects and have improved patient compliance. SUMMARY OF THE INVENTION

The present specification relates to a topical skin care compositions comprising niacinamide, glycyrrhetinic acid, filagrinol and pseudo-ceramide and process for preparing such compositions.

In one aspect, the present specification relates to a topical skin care composition comprising:

(i) niacinamide,

(ii) glycyrrhetinic acid,

(iii) filagrinol,

(iv) pseudo-ceramide, and

(v) one or more pharmaceutically acceptable excipients.

In another aspect, the present specification relates to a topical skin care composition comprising:

(i) niacinamide,

(ii) glycyrrhetinic acid,

(iii) filagrinol,

(iv) pseudo-ceramide, and

(v) one or more butters.

In yet another aspect, the present specification relates to a topical skin care composition comprising:

(i) niacinamide,

(ii) glycyrrhetinic acid,

(iii) filagrinol,

(iv) pseudo-ceramide,

(v) one or more butters,

(vi) one or more emulsifying agents, and

(vii) water.

In yet another aspect, the present specification relates to use of topical skin care composition for treating and preventing psoriasis, atopic dermatitis or other skin disorders such as dry skin, eczema, red skin, inflamed skin, and/or cracked skin, for the relief of itching and the restoration of the affected areas of skin to a normal condition.

DESCRIPTION OF THE INVENTION

The present specification relates to a topical skin care compositions comprising niacinamide, glycyrrhetinic acid, filagrinol and pseudo-ceramide and process for preparing such compositions.

In one aspect, the present specification relates to a topical skin care composition comprising:

(i) niacinamide,

(ii) glycyrrhetinic acid,

(iii) filagrinol,

(iv) pseudo-ceramide, and

(v) one or more pharmaceutically acceptable excipients.

In another aspect, the present specification relates to a topical skin care composition comprising:

(i) niacinamide,

(ii) glycyrrhetinic acid,

(iii) filagrinol,

(iv) pseudo-ceramide, and

(v) one or more butters.

In yet another aspect, the present specification relates to a topical skin care composition comprising:

(i) niacinamide,

(ii) glycyrrhetinic acid,

(iii) filagrinol,

(iv) pseudo-ceramide,

(v) one or more butters,

(vi) one or more emulsifying agents, and (vii) water.

As used herein, the term "topical" is used in its conventional sense to mean delivery of a topical drug or pharmacologically active agent to the skin or mucosa, as in, for example, the treatment of various skin disorders. Topical administration, in contrast to transdermal administration, primarily provides a local rather than a systemic effect.

The term "composition" is intended to encompass a combination including active ingredients and pharmaceutically acceptable excipients. The term "excipient" or "pharmaceutically acceptable excipient" means a component of a pharmaceutical product that is not a pharmacologically active ingredient, such as filler, diluent, carrier, preservative, etc. The excipients that are useful in preparing pharmaceutical compositions are generally safe, non- toxic, and are acceptable for veterinary use as well as human pharmaceutical or cosmetic use. The term includes both one and more than one such excipients. The skin care composition of the present specifications may be in the form of lotions, liquids, creams, gel, etc. that are suitable for topical administration.

The topical skin care compositions of the present specification comprise niacinamide, glycyrrhetinic acid, filagrinol, pseudo-ceramide and pharmaceutically acceptable excipients.

As used herein, the term "niacinamide" includes niacinamide or any pharmaceutically acceptable salts or esters or derivatives thereof. The amount of niacinamide employed in the skin care composition is in the range of 0.5 % to 5% (w/w), 1% to 4% (w/w) of total composition, e.g. 4% (w/w).

As used herein, the term "glycyrrhetinic acid" includes glycyrrhetinic acid or any pharmaceutically acceptable salts or esters or derivatives thereof. The amount of glycyrrhetinic acid employed in the skin care composition is in the range of 0.1 % to 5% (w/w), 1% to 4% (w/w) of total composition, e.g. 1% (w/w).

The amount of filagrinol employed in the skin care composition is in the range of 0.3% to 10% (w/w), 4-8% to 4% (w/w) of total composition, e.g. 8% (w/w). The amount of pseudo-ceramide employed in the skin care composition is in the range of 0.1% to 5% (w/w), 0.1 % to 3% (w/w) of total composition, e.g. 1% (w/w).

Useful pharmaceutical acceptable excipients of the present specification include, but are not limited to vehicles or diluents, plasticizers, film forming agents, chelating agents, thickening or gelling agents, neutralizers, emulsifying agents, emollients, humectants, preservatives, antioxidants, solvents, fragrance imparting agents, and the like, including any combinations of two or more thereof.

The skin care compositions of the present specification include one or more butters as an excipient. Butters play a main role in healing the conditions, due to their unique fatty acid profiles and high contents of vitamins E and A that contribute to its protective and hydrating properties. Some butters also have natural UV protection which helps in effective skin moisturization and visibly reduces the appearance of fine lines and wrinkles. They will help to nourish and rejuvenate skin cells making the skin feel soft, silky and smooth. Representative examples of the butters that are usable in the context of present invention include, but are not limited to, cocoa butter, Shea butter, mango butter, aloe butter, pumpkin seed butter, coconut lime verbena body butter, cranberry butter, etc.

Shea butter has a unique fatty acid profile and the high content of vitamins E and A contributes to its protective and hydrating properties. Clinical trials have shown that Shea butter provides natural ultraviolet (UV) radiation protection, is an effective skin moisturizer, and visibly reduces the appearance of fine lines and wrinkles. It may be used in concentrations ranging from about 0.1% to about 5 % w/w.

Cocoa butter is the cream-colored fat extracted from cacao seeds (cocoa beans) and used to add flavor, scent, and smoothness to chocolate, cosmetics, tanning oil, soap, and a multitude of topical lotions and creams. Cocoa butter has been called the "ultimate moisturizer," and has been used to keep skin soft and supple. It is one of the most stable, highly concentrated natural fats known, and melts at body temperature so that it is readily absorbed into the skin. Cocoa butter is often recommended for treatment of skin conditions such as eczema and dermatitis. When applied topically, it creates a barrier between sensitive skin and the environment and also helps retain moisture. In addition, cocoa butter contains cocoa mass polyphenol (CMP), a substance that inhibits the production of the immunoglobulin IgE, known to aggravate symptoms of both dermatitis and asthma. It may be used in concentrations ranging from about 0.1% to about 5% w/w.

Mango butter has natural emollient properties, high oxidative ability, wound healing, and regenerative activity. Mango butter has been traditionally used in the rainforests and tropics for its skin softening, soothing, moisturizing and protective properties, and to restore flexibility and reduce degeneration of skin cells. It has a protective effect against UV radiation. It is used to treat eczema and dermatitis. It may be used in concentrations ranging from about 0.1% to about 5% w/w.

Aloe butter is a soft solid butter at room temperature, which melts on contact at skin temperatures. Aloe butter may be used for cutaneous dryness, to assist in moisturization after exposure to sun and other harsh elements. It may be used in concentrations ranging from about 0.1% to about 5% w/w.

The skin care compositions of the present specification include one or more emulsifying agents. Examples of emulsifying agents that are useful for preparing compositions of the present specification include, but are not limited to, sodium lauryl sulfate, sodium laureth sulfate (or sodium lauryl ether sulfate), polysorbate 60, polysorbate 80, emulsifying wax, fatty acids having 12-18 carbon atoms, such as undecylenic acid, lauric acid, myristic acid, palmitic acid, stearic acid, cetostearyl alcohol, isostearic acid, aracel, oleic acid, hydroxyoleic acid, linoleic acid, and their derivatives, glyceryl stearate, propylene glycol monostearate, sorbitan monolaurate, sorbitan monopalmitate, sorbitan monostearate, sorbitan tristearate, sorbitan monooleate or sorbitan trioleate or mixtures thereof. In some embodiments, the emulsifying agent includes mixture of glyceryl stearate and polyethylene glycol-100 stearate (ARLACEL 165). Useful emulsifying agents further include cetyl alcohol, acacia, carbomers, carrageenan, cetostearyl alcohol, ceresin wax, and any combinations thereof. The skin care compositions of the present specification may comprise a solubilizer. Suitable solubilizers include hexylene glycol, propylene glycol, polyethylene glycol or mixtures thereof. Preferred solubilizer includes propylene glycol. The amount of solubilizers employed in the composition is in the range of 1% to 20% (w/w) of total composition, e.g. 3% (w/w), 5% (w/w).

The skin care compositions of the present specification may comprise an emollient. Suitable emollients include, for example, stearyl alcohol, glyceryl monooleate, glyceryl monoricinoleate, glyceryl monostearate, cetyl alcohol, ispropyl isostearate, stearic acid, isobutyl palmitate, isocetyl stearate, oleyl alcohol, isopropyl laurate, hexyl laurate, decyl oleate, octadecan-2-ol, isocetyl alcohol, cetyl palmitate, dime thy lpolysiloxane, di-n-butyl sebacate, isopropyl palmitate, isopropyl stearate, butyl stearate, polyethylene glycol, triethylene glycol, lanolin alcohol, sesame oil, coconut oil, arachis oil, castor oil, acetylated lanolin alcohols, petroleum, mineral oil, butyl myristate, isostearic acid, palmitic acid, isopropyl linoieate, lauryl lactate, myristyl lactate, decyl oleate, myristyl myristate, and mixture thereof. In some embodiments the emollient includes mixture of polysorbate 80, cetyl acetate, stearyl acetate, oleyl acetate acetylated lanolin alcohol (Crodalan AWS).

The skin care compositions of the present specification may comprise aqueous base as required. The oil phase excipients include the butters, emollients, emulsifying agents and others. The emulsifying agents help the dispersion of oil phase and aqueous phase. The amount of water employed in the compositions is in the range of 30% to 80% (w/w) of total composition, e.g. 50% (w/w), 65% (w/w).

The skin care compositions of the present specification may further comprise a humectant. Examples of humectants that are useful in the context of the present invention include, but are not limited to, glycerin, propylene glycol, cyclomethicones, dimethicones, sorbitol, xylitol, urea, sugars and starches, sugar and starch derivatives (e.g., alkoxylated glucose), D-panthenol, hyaluronic acid, lactamide monoethanolamine, acetamide monoethanolamine, 2-pyrrolidone-5- carboxylic acid, urea, and any mixtures thereof. The skin care compositions of the present specification may further comprise a thickener. Suitable thickeners include carboxylic acid polymers like carbomers (e.g. Carbopol.RTM. 954), acrylates/vinyl neodecanoate crosspolymer (e.g. Aculyn 38), natural gums (e.g. guar, xanthan), cellulose derivatives (e.g. carboxy methylcellulose, methyl cellulose), PEG 6000, polyvinyl alcohol, polyamide-5 and mixtures thereof.

The skin care compositions of the present specification may comprise one or more preservatives. Examples of preservatives include, but are not limited to, benzalkonium chlorate, bronopol, chlorhexidine, chlorocresol and its derivatives, mixture of methylisothiazolinone and phenoxyethanol (NEOLONE™ PE), phenoxyethanol, ethylic alcohol, phenethylic alcohol, potassium sorbate, diazolidinylurea, benzylic alcohol, parabens alone or in mixture.

The skin care compositions of the present specification may comprise one or more pH adjusting agents. Such ingredients include dermatologically acceptable acids, bases and buffers. The pH of the compositions can range from about 4 to about 10, but preferably is in the range of about 5 to about 8, in particular from about 5 to about 7.5.

The skin care compositions of the present specification may contain additional ingredients to improve the composition. Such ingredients include film formers, chelating agents, neutralizers, antioxidants, buffering agents. Examples of such ingredients are well known in the art.

The topical skin care compositions of the present specification can be manufactured using a method comprising:

a) preparing an oil phase by combining the oil soluble ingredients;

b) preparing an aqueous phase by combining water soluble ingredients in warm water, and adding a preservative; and

c) combining the aqueous phase of step b) and the oil phase of step a), followed by homogenization.

The skin care compositions of the present specification can be part of a kit or device and may be filled into tubes, jars, bottles, aerosol containers, and any other forms of packaging that facilitate application topically. The compositions are meant to be applied topically, either manually or by using a convenient applicator, for patient compliance and ease of application. The dose, number, and frequency of applications can be determined by a person skilled in the art of treating conditions, such as a physician, a dermatologist, and the like.

Laminated tubes may be used for packaging. The features and advantages of laminated tubes include ability to retain smoothness, flexibility and softness, increase in product shelf life, excellent barrier properties, excellent sealability, resistance to print bleeding, tamper evident closures with nozzle seals available, and hot foil stamping. HDPE tubes may also be used for packaging. Examples are pre -printed monolayer plastic tubes made of LDPE/LLDPE blends by extrusion processes and fitted with snap-on flip caps made up of polypropylene.

The skin care composition of the present specification can be used for treating and preventing psoriasis, atopic dermatitis or other skin disorders such as dry skin, eczema, red skin, inflamed skin, and/or cracked skin, for the relief of itching and the restoration of the affected areas of skin to a normal condition.

The skin care compositions of present specification were subjected to accelerated and long term stability studies.

The specification will now be described in greater detail by reference to the following non-limiting examples.

EXAMPLES

Process:

Oil phase preparation:

1. Shea Butter, aloe Butter, mango Butter, cocoa Butter, cetyl alcohol, stearic acid and emulsifying wax were taken in to the dry oil phase vessel and heated to 70°C +5°C until it melted completely.

2. Hydroxypropyl Bispalmitamide MEA (ceramide PC- 104) was added to the above mixture. 3. Cyclomethicone and dimethicone were added to the oil phase (step 2) and continued mixing for 5 min.

4. Filagrinol was added to the oil phase of step 3 and mixed well.

Aqueous phase preparation:

5. Purified water was taken in a main manufacturing vessel and heated to 70°C+5°C.

6. Disodium edetate was added to the aqueous phase of step 5 and mixed for 5 minutes.

7. Propylene glycol and glycerin were added to the aqueous phase of step 6 and mixed for 5 min while maintaining the temperature at 70°C+5°C.

Lotion Preparation:

8. Oil phase obtained in step 4 was added to the aqueous phase obtained in step 7 under stirring and homogenization.

9. Zinc Oxide was dispersed in purified water at 60°C+2°C. Zinc oxide dispersion was added to the product obtained in step 8 with mixing and homogenization.

10. Niacinamide was dissolved in water and added to the product obtained in step 9 under stirring.

11. Glycyrrhenitic acid, NEOLONE™ PE or phenoxyethanol and fragrance were added and stirred well until uniformly distributed to obtain the final composition.

S. No Ingredient Example 3

(%w/w)

Oil phase

1 Shea Butter 2

2 Mango Butter 1

3 Cocoa Butter 1

4 Aloe Butter 1

5 Filagrinol 8

6 Hydroxypropyl Bispalmitamide MEA ( Ceramide PC-104) 1

7 Cetyl Alcohol 4

8 Arlacel-165 (Glyceryl stearate and PEG- 100 stearate) 8.0

9 Span-60 (Sorbitan monostearate) 3

10 Cyclomethicone 3

11 Dimethicone 1

12 Butlyated hydroxy toluene 0.1

Aqueous phase

12 Niacinamide 3

13 Glycyrrhenitic acid 2

14 Phenoxyethanol 1

15 Glycerin 5

16 Disodium EDTA 0.2

17 Zinc Oxide 0.2

18 Fragrance 0.1

19 Purified water qs to 100

Process:

1. Shea butter, aloe butter, mango butter, cocoa butter, cetyl alcohol, Arlacel-165 and Span- 60 were taken in to the dry oil phase vessel and heated to 70°C +5°C until it melted completely.

2. Hydroxypropyl bispalmitamide MEA (ceramide PC-104), cyclomethicone, dimethicone, butlyated hydroxy toluene were added to the above mixture and mixed well. Subsequently filagrinol was added to the mixture and mixed uniformly. 3. Purified water was taken in a main manufacturing vessel and heated to 70°C+5°C and disodium edetate, glycerin were added sequentially and mixed for 5 minutes.

4. Oil phase obtained in step2 was added to the aqueous phase obtained in step3 under stirring and homogenization.

5. Aqueous zinc oxide dispersion was added to the product obtained in step 4 with mixing and homogenization.

6. Niacinamide was dissolved in water and added to the mixture with stirring.

7. Glycyrrhenitic acid, phenoxyethanol and fragrance were added and stirred well until uniformly distributed to obtain the final composition.

19 Disodium EDTA 0.2 0.2

20 Xanthan gum 0.15 —

21 Citric acid 0.5 0.15

22 Sodium citrate 0.9 0.78

23 Fragrance 0.2 0.2

24 Purified water qs to 100 qs to 100

Process:

1. Shea butter, aloe butter, mango butter, cocoa butter, ceto-stearyl alcohol, lanolin alcohol, oleyl alcohol, crodalan AWS and Span-60 were taken in to the dry oil phase vessel and heated to 70°C +5°C until it melted completely.

2. Hydro xypropyl bispalmitamide MEA (ceramide PC- 104), filagrinol, cyclomethicone, butylated hydroxy toluene were added to the above mixture and mixed well.

3. Purified water was taken in a main manufacturing vessel and heated to 70°C+5°C and disodium edetate, glycerin, citric acid, sodium citrate were added sequentially and mixed for 5 minutes.

4. Oil phase obtained in step2 was added to the aqueous phase obtained in step3 under stirring and homogenization.

5. Aqueous zinc oxide dispersion was added to the product obtained in step 4 with mixing and homogenization.

6. Niacinamide was dissolved in water and added to the mixture with stirring.

7. Glycyrrhenitic acid, phenoxyethanol, xanthan gum, fragrance were added and stirred well until uniformly distributed to obtain the final composition.

5 Filagnnol 8

6 Hydroxypropyl Bispalmitamide MEA ( Ceramide PC- 104) 1

7 Ceto-stearyl Alcohol 0.5

8 Arlacel-165 (Glyceryl stearate and PEG-100 stearate) 2

9 Span-60 (Sorbitan monostearate) 0.25

10 Medium chain triglycerides 2

11 Dimethicone 2

Aqueous phase

12 Niacinamide 4

13 Glycyrrhenitic acid 1

14 Methyl paraben 0.2

15 Propyl paraben 0.02

16 Butylated hydroxy toluene 0.1

17 Sorbitol solution 70% 2.5

18 Disodium EDTA 0.2

19 Zinc Oxide 0.2

20 Carbomer (980) 0.1

21 Propylene glycol 5.0

22 Trolamine 0.1

23 Fragrance 0.2

24 Purified water qs to 100

Process:

1. Shea butter, aloe butter, mango butter, cocoa butter, ceto-stearyl alcohol, Arlacel-165 and Span-60 were taken in to the dry oil phase vessel and heated to 70°C +5°C until it melted completely.

2. Hydroxypropyl bispalmitamide MEA (ceramide PC- 104), dimethicone, medium chain triglyceride were added to the above mixture and mixed well. Subsequently, filagrinol was added to the mixture and mixed uniformly.

3. Purified water was taken in a main manufacturing vessel and heated to 70°C+5°C and disodium edetate, propylene glycol, sorbitol solution, methyl paraben, propyl paraben, butylated hydro xyl toluene were added sequentially and mixed for 5 minutes. 4. Oil phase obtained in step2 was added to the aqueous phase obtained in step3 under stirring and homogenization.

5. Aqueous zinc oxide dispersion was added to the product obtained in step 4 with mixing and homogenization.

6. Niacinamide was dissolved in water and added to the mixture with stirring.

7. Glycyrrhenitic acid, and carbomer, trolamine, fragrance were added and stirred well until uniformly distributed to obtain the final composition.

Purified water

Process:

1. Shea butter, aloe butter, mango butter, cocoa butter, cetyl alcohol, Arlacel-165 and Span- 60 were taken in to the dry oil phase vessel and heated to 70°C+5°C until it melted completely.

2. Hydroxypropyl bispalmitamide MEA (ceramide PC-104), cyclomethicone, polyamide-5, butylated hydroxy toluene were added to the above mixture and mixed well. Subsequently, filagrinol was added to the mixture and mixed uniformly.

3. Purified water was taken in a main manufacturing vessel and heated to 70°C+5°C and disodium edetate, zinc oxide, citric acid monohydrate, and sodium citrate were added sequentially and mixed for 5 minutes. Subsequently, glycerol was added and mixed uniformly.

4. Oil phase obtained in step2 was added to the aqueous phase obtained in step3 under stirring and homogenization.

5. Niacinamide was dissolved in water and added to the mixture with stirring.

6. Glycyrrhenitic acid, phenoxyethanol and fragrance were added and stirred well until uniformly distributed to obtain the final composition.

Stability study

The stability of the topical skin care compositions of present specification were evaluated through accelerated stability studies. The composition was prepared according to the formula and process of example 7, and was subjected to stability study at various temperature and humidity conditions, and the pH, viscosity and assay were measured at different time points. The composition was found to be stable at accelerated conditions. Table 1 represents the study result data.

Table 1 : Stability study

6M Complies complies Complies 101.9 89.4 92.1 5.87 35310