INTRODUCTION:

Topical medication delivery is described as the application of a dosage form to the skin for the direct treatment of integumentary and related disorders, with the goal of constraining the drug's pharmacological or other action to the skin's surface¹. Creams are used for a variety of functions, including cosmetic purposes such as washing, beautifying, and moisturising, as well as protecting the skin from bacterial and fungal infections and providing a healing effect for cuts, burns, and wounds². Creams are semisolid, thick dosage forms used for topical administration to the skin. They can be used on the surface of the eye, or nasally, vaginally, or rectally for medicinal, protective, or cosmetic purposes³.

The cosmetic and pharmaceutical industries provide a variety of skin care products as well as a variety of methods to protect, clean, soothe, fortify, and treat the skin in order to maintain it in "excellent shape"⁴. The major purpose of such excipients is to limit the amount of absorption, maintain viscosity, improve stability, and raise the bulk of the formulation⁵.

Skin creams are classed according to the following criteria:

· Purposes: for example, cleansing, foundation, massage, and so forth.

· Characteristic properties, such as cold creams, disappearing creams, and so on.

· Emulsion type or nature⁶.

As a topical preparation, creams are an important component of cosmetics. Creams can be used to wash the face in a variety of ways. In circumstances of rough, dry, and chapped skin, cosmetic creams act as a skin feeder⁷. Creams were made in ancient times by simply mixing two or more ingredients with water as the solvent ⁸. The biological features of the stratum corneum directly contribute to the maintenance and maintenance of healthy skin⁹. Women and men both use cosmetics such as lotions, gels, and colognes on a regular basis¹⁰.

Several research have looked into the ability of nanoparticles to enter the stratum corneum. The method and determinants of their penetration are poorly understood¹¹. Because the skin works as a natural as well as protective barrier, using a topical or transdermal medicine delivery device might be difficult at times¹². When compared to alternative routes of medication delivery, minimally or non-invasive drug delivery through the skin has various advantages, and they also play an essential role in several medical routines¹³. Film-forming formulations are a very desirable type of prolonged release product. Penetration and permeation tests on various formulations suggest that they could be useful as transdermal medicinal devices¹⁴.

The attainment of authentic and suitable drug delivery of treatments through the skin is highly suggested in order to reduce the impact of systemic toxicity of the number of medications used in the treatment of local, acute, and chronic inflammatory reactions¹⁵.

Different volume of stearic acid and cetyl alcohol were used to produce several types of herbal creams, such as oil in water herbal creams¹⁶. Ayurvedic, herbal, or medically aided cream formulations are common, and individuals use them to treat a variety of skin problems¹⁷. Except for transdermal delivery systems (TDS) and transdermal patches, which will be discussed individually, the term topical drug refers to all preparations that are delivered through the skin¹⁸.

Skin Anatomy and Physiology:

The largest exterior defence mechanism is the skin. Sensation, insulation, temperature regulation, vitamin D metabolism, and vitamin B folate maintenance are among its other roles. The skin is the largest point of contact between the body and the environment, with Thermoregulation, protection of the body against physical, chemical, and microbiological harm, and loss of water and other chemicals are only a few of the activities¹⁹.

Fig. 1: Skin anatomy

Anatomy:

The outermost layer is called epidermis, the middle layer is called dermis and the inner most layer is hypodermis¹.

Skin layers:

1. Epidermis:

It is made up of epithelial cells. It is possible to find both living and dead cells among these cells¹. The epidermis lacks blood vessels and nerve endings, but the deeper layers of it arise in interstitial fluid, that serves oxygen and nutrition while also draining as lymph.

The epidermis is consists of five layers, ranging from the interior to the outside;

a. Stratum germinativum (basal layer)

b. Stratum spinosum

c. Stratum granulosum

d. Stratum lucidumand stratum corneum

e. Stratumcorneum is the most outer layer of epidermis and posess a thickness of around 10-20μm in dry state and 40μm in hydrated form and becomes swollen¹.

2. Dermis:

The dermis is found beneath the epidermis and is made up of a lot of elastin fibres that allow the skin to stretch and a lot of collagen that gives it strength. The dermis is important for temperature regulation. Pressure and discomfort sensations are caused by the presence of nerves in this area¹. Collagen fibres bond to water and provide suppleness to the skin, but as this ability deteriorates with age, wrinkles appear⁷.

Types of cells found in dermis layer are:

· Fibroblasts: These are the collagen producing cells

· Macrophages: Also called as scavenger cells

· Mast cells: They are cause the immunological reactions and interacts with eosinophils¹.

3. Hypodermis:

Hypodermis is the inner most layer of skin. Sweat glands, sebaceous glands and hair follicles tends to be found in epidermis but they stem from dermis¹.

Development of the Stratum Corneum (SC):

The SC represents the epidermis's most superficial and final layer of development. The sequence of events occurs as keratinocytes move upward after forming in the epidermis' multiple layers (stratum). When keratinocytes reach the stratum granulosum, they undergo a series of changes before being turned into corneocytes, which maintains the SC in place until the final step of desquamation.

The following is the order of epidermal change and the layers involved:

1. Cellular proliferation with the development of keratinocytes in the basal layer (stratum basal);

2. Keratinocyte squamous differentiation in the spinous layer (stratum spinosum);

3. Subcutaneous development with the transformation of keratinocytes to corneocytes in the granular layer (statum granulosum) and the compacting layer (stratum compactum);

4. Stratum Corneum (into the atmosphere)^1,3,4,7,9.

Functions of Skin:

a) Protection: Langerhans cells are a part of the adaptive immune system and serves as a obstacle between the inner and outer environment, protecting the body from numerous microorganisms and injury.

b) Sensation: The somatosensory system and haptics refer to a group of nerve endings that respond to heat and cold, touch, pressure, vibration, and tissue injury.

c) Heat regulation: Skin has a far larger blood supply than it requires, control of energy loss through radiation, convection, and conduction. Dilated blood vessels improve perfusion and heat loss, whereas constricted blood vessels decrease cutaneous blood supply and help to keep heat in the body.

Skin Diseases:

a) Vitiligo:

Vitiligo is a condition in which some areas of the skin lose their pigmentation and become significantly paler than normal skin. It is widespread, affecting approximately 1% of the world's population. Melanin is a substance that gives our skin its usual colour⁷.

Fig. 2: Vitiligo skin disorder

b) Scabies:

Human scabies mites create scabies, which is an extremely itchy derma disorder. It affects people at all ages, but it is more common in children and the elderly. Scabies is caused by parasitic mites that are as little as a pinhead. Scratches and red scaly regions characterise the scabies rash, which can later get infected and develop small pus spots⁷.

Fig. 3: Scabies skin disorder

c) Rosacea:

It's a chronic dermatologic disorder marked by erythema in the centre of the face, flushing, and, in many cases, inflammatory lesions. Sensitive skin is a most common symptom of rosacea, with patients describing symptoms such as burning, stinging, and itching. Although there are numerous medicaltherapies and physical methods for treating rosacea, skin care is an essential component of good rosaceamanagement²⁰.

Fig. 4: Rosacea skin disorder

d) Psoriasis:

It is a prevalent skin condition that affects nearly 2% of the population. It affects both men and women of all ages. It is not contagious and does not leave a scar on the skin.

Fig. 5: Psoriasis skin disorder

e) Melanoma:

It's a skin cancer that affects the pigment cells. If caught early enough, the prognosis is usually favourable. It is not a contagious disease. Melanoma is derived from the Greek word melas, which means "black."

Fig. 6: Melanomaskin disorder

f) Eczema (Atopic Eczema): Eczema atopica is a skin inflammatory disorder. Eczema, asthma, seasonal rhinitis, and hay fever are examples of atopic disorders, which typically have a genetic basis. Eczema is a skin disorder that creates redness, blistering, weeping, crusting, scaling, thickness, and sometimes pigmentation in the upperlayer of the skin⁷.

Fig. 7: Eczema skin disorder

Wound and Wound Healing:

Wound healing is a complicated process that includes three stages: hemostasis and inflammation, proliferation or fibroplasia, and remodelling. A good wound healing product is one that is found to be successful in reducing inflammation, enhancing fibroplasia, and speeding up the remodelling of the healing tissue in the shortest amount of time and with the fewest side effects. To be clinically comfortable, the healed wound should have the smallest possible scar tissue size and the best possible biomechanical function. Wounds are described as a breach in the cellular, anatomical, or functional continuity of the deep skin tissue or living tissues^2,7,21.

Wounds can be classified mainly on the basis of mode of infliction and causative agent as:

1. Closed wound- contusion, closed fracture, etc.

2. Open wound-

a. Sharp cut.

b. Laceration.

c. Abrasion.

d. Avulsion.

e. Crush wound.

f. Punctured wound.

g. Bite wound.

h. Burn wound.

Topical Drug Delivery System:

Topical drug delivery is the application of a drug-containing preparation to the skin to treat cutaneous disorders (e.g. acne) or cutaneous manifestations of a general disease (e.g. psoriasis) with the goal of limiting the drug's pharmacological or other effects to the skin's surface or within the skin¹. The main aim of this form of distribution is to confine the drug's pharmacological or other action to the skin's surface or within it. For the distribution of diverse dosage forms, three major modes are extensively used: topical, regional, and transdermal⁵.

Topical dosage forms are distinguished into following major categories:

· Solid topical dosage form

· Dusting powder

· Semisolid topical dosage form

· Cream

· Ointment

· Gel

· Paste

· Liquid topical dosage form

· Lotion

· Liniment⁵

Topical delivery can also be defined as the applying a drug-containing dosage form on the skin to treat a skin disorder or general disease (e.g. psoriasis) with the aim of achieveing the pharmacological effect of the drug to the skin's surface or within the skin. While semisolid formulations in all their forms dominate the system for topical delivery, foams, sprays, medicated powders, solutions, and even medicated cream^7.

Chemicals are prevented from penetrating the epidermis by SC.

Intercellular lipids are organised in a head-to-head and tail-to-tail pattern in the SC. This results in both lipophilic (tail-to-tail) and hydrophilic (head-to-head) pores that can allow NP to penetrate²².

The size of the penetrant molecule is believed to be one of the most important elements in all types of penetration processes. The size and composition of nanoparticles that may come into contact with human skin might vary greatly. Pharmaceutical nanosystems, such as solid lipid nanoparticles (SLN) or liposomes, are typically 25 to 50 nm in size¹⁹.

Solutions (for which release testing is not recommended), collodion, suspensions, emulsions (e.g., lotions), semisolids (e.g., foams, ointments, pastes, creams, and gels), solids (e.g., powders and aerosols), and sprays are all examples of topical dose forms. These dose types have vastly differing physical qualities from one another. TDS patches, sometimes known as transdermal patches, are devices that are applied on the skin and vary in composition and manufacture method. As a result, they use various techniques to release their active components^5,7,8,18.

Ideal Characteristics of Topical Drug:

· Water solubility: Before a medicine may penetrate a membrane, it must first be dissolved in aqueous bodily fluids.

· Log P: The medication must have enough lipophilicity to pass through membranes.

· Molecular weight: Drugs with a higher molecular weight may have a difficulty crossing membranes.

· Solution stability: Drugs in solution tend to hydrolyze, oxidise, photolyze, or otherwise deteriorate.

· Enzymatic degradation: Before reaching their target, several medications may be significantly destroyed by a variety of enzymes.

· Receptor location: Targeting intracellular drug receptors or receptors in the brain or posterior eye is difficult.

· Selectivity: Poor selectivity for the targeted location can result in significant toxicity in some medications²³.

Topical formulations have three main functions:

· Because of its emollient characteristics, it helps to keep skin hydrated.

· To protect an undamaged or injured portion of the skin from the external environment or to heal it.

· To apply medication directly to the skin¹.

Advantages of Topical Drug Delivery System:

· First-pass metabolism is avoided.

· Convenient and simple to use.

· Disadvantages of intravenous therapy, as well as the various conditions such as pH fluctuations, enzyme presence, gastric emptying time, and so on.

· Continuous drug input achieves efficacy with reduced total daily drug dosage.

· Prevent medication levels from fluctuating between and within patents⁷.

Disadvantages of Topical Drug Delivery System:

· Drug and/or excipients may cause contact dermatitis on the skin;

· Some drugs have poor permeability through the skin; • Allergic reactions are possible;

· Only used for the drugs that require a very low plasma concentration for action;

· The medications may be denatured by an enzyme in the epidermis.

· Larger-particle-size drugs are more difficult to absorb through the skin⁸.

CREAMS:

Creams are a type of topical product that can be applied to the skin. Creams are "viscous liquid or semi-solid emulsions of either the oil-in-water or water-in-oil type," the consistency of which varies depending on the amount of oil and water used. Creams can be used for a variety of cosmetic objectives, including cleansing, beautifying, improving looks, and protecting as well as medicinal purposes. These items are intended to be used topically to increase drug delivery to specific skin locations for skin diseases. Creams are classified as pharmaceutical products since they are made using procedures developed in the pharmaceutical sector; both unmedicated and medicated creams are widely used to treat a variety of skin problems and dermatoses. They are made up of one or more drug compounds that have been dispersed in a suitable base to form a homogeneous emulsion².

Creams, ointments, and pastes are examples of semisolid formulations. Cream is an oil-in-water emulsion that is applied to the skin. Emulsions are a type of dispersion system that consists of two insoluble, thermodynamically stable phases: continuous and scattered. If the dispersed phase is oil, the emulsion is water-in-oil, and vice versa. Simpleemulsion is the name for this sort of emulsion. Multiple emulsion refers to a system in which a simple emulsion is further dispersed in a dispersed phase medium. Emulsions are classified into macro and microemulsions based on the size of the scattered phase globules. Emulsions are widely employed as a vehicle for medication administration, particularly across the skin, due to their features. Waterin-oil (W/O) emulsions are more widely utilised for the treatment of dermatological issues, particularly for dry skin²⁴. Creams are semisolid dosage forms that are applied over the skin, deposited on the surface of the eye, or administered nasally, vaginally, or rectally for medicinal or protective purposes, as well as for cosmetic purposes. These preparations are utilised for the localised effects caused by medication penetration into the internal layer of skin or mucousmembrane at the place of application. The skin is the target organ for these products, which are designed to deliver drugs into the skin for the treatment of cutaneous illnesses. Although W/O creams are more hard to work with, many medications used in creams are water hating and will release more quickly from a water-in-oil cream than from an oil-in-water cream. Water-in-oil creams are more hydrating because they create an oily barrier that prevents loss of water from the stratum corneum, the skin's outermost layer^3,4.

Creams (water-in-oil emulsion) and lotions (oil-in-water emulsion) are the most common kind of moisturisers. The inclusion and relative concentration of heavier occlusive agents such as petrolatum and lanolin derivatives, the intrinsic properties of various emollients and humectants that may be included in some products, and the oil-water ratio all influence the final formulation's "heaviness." Night creams are an example of a product that is designed to have a thicker formulation. Specific components are frequently blended in formulations to correspond to specific "skin types," such as dry, normal, or oily complexions. This is accomplished by adjusting the oil-water ratios and changing the occlusive agent's heaviness by the use of certain emollients that may be protective, fattening, dry, or astringent in their inherent qualities²⁵.

Creams and pastes are multiphasic systems in which the vehicle elements are not miscible or dissolved in each other; instead, one phase disperses into the other. Both hydrophilic and lipophilic versions are available for all formats²⁶.

Classification of Creams:

All the skin creams can be classified on different basis:

1. According to their function, e.g. cleansing, foundation, massage, etc.

2. According to their characteristics properties, e.g. cold creams, vanishing creams,etc.

3. According to their nature or type of emulsion.

Types of creams according to function, characteristic properties and type of emulsion:

1. Make-up creams, which are mostly o/w emulsions. It's a cream-based product that gives the skin a moisturised, smooth finish (either stain matte or bright). It hydrates the skin, makes it sweat-resistant, and gives it a dewy sheen.

a. Vanishing creams: These creams are so named because they appear to vanish when applied onto the skin. Stearic acid is used in these compositions. The cream leaves a dry but tacky residue coating on the skin after application.

b. Foundation creams: These creams are used as a make-up foundation basis. It's a multi-colored make-up that's applied on the face to create an even, uniform hue that matches the complexion, conceal blemishes, and adjust skin tones.

2. Cleansing creams: These creams mostly used for body washing, personal hygiene, and cosmetic enhancement, all of which are important in the cosmetics sector. Cleansing creams or lotions can be used to remove make-up, dirt, and oil from the face and neck.

3. Winter creams: These are w/o formulations in which the oil concentration is greater than the water content. These lotions are used to treat chapped and dry skin. Moisturizer or moisturizing creams are cold cream. Emollient properties are required in cold cream. When used, it should provide a cooling feeling and leave no occlusive oil layer on the skin.

4. Night creams or massage creams: These creams are primarily used to hydrate the skin or to cure dry skin. Night creams are creams that are applied to the skin and left on for a few or many hours over night. Massage creams are emollient creams that are applied to the skin with massage to act as an emollient.

5. Skin protection creams: These are smooth, thick-bodied creams that are developed to establish an invisible, homogeneous protective film barrier on the skin. It aids in the preservation of the skin's barrier against pollutants that may irritate it (contact dermatitis and occupational dermatitis). Strengthens the skin's natural characteristics and keeps normal to mixed skin in balance.

6. Hand and body creams: One of the first areas to exhibit signs of ageing is the hands. We have a habit of washing our hands multiple times a day to remove dampness. Cream softens and prevents the skin while also making it appear younger.. Since the skin on our palms and fingers needs oil to stay supple and to prevent it from chapping and cracking, it is sensible to use hand creams that puts plenty of oil back in. It is usedon the hands more than other parts of the body^2,4,6,7.

Types of Skin Creams:

They are classified into two types:

· Oil-in-Water (O/W) creams are made up of minute droplets of oil spread in a continuous phase, and an oil-in-water (O/W) emulsion is one in which the oil is dispersed as droplets throughout the aqueous phase.

· Water-in-Oil (W/O) creams are made up of minute water droplets suspended in a continuous oily phase. The emulsion is of the water-in-oil (W/O) type when water is the dispersed phase and oil is the dispersion medium.

General Ingredients Used in Preparation of Creams:

The raw materials which are used in a manufacturing of skin creams include:

· Water is the cheapest and most readily available option. Water is used as a solvent in skin treatments to dissolve other ingredients. Creams are made with water that is free of toxins, pollution, microorganisms, and other contaminants. Water can also create emulsions, depending on how much water is used in the formulation. These emulsions are sometimes referred to as oil-in-water emulsions and other times as water-in-oil emulsions, depending on the amounts of water and oil phase employed. It acts as a liquefier for the cream's other ingredients.

· Oil, fats and waxes: Oil, fats and waxes are one of the essential portions of the cream. Waxes act as an emulsifier, fats act as a thickener and oil act as a perfuming agent, preservative, etc. according to its function.

· Mineral oil is made up of hydrocarbons that are obtained from petroleum oil. Mineral oil is a clear, odourless, highly refined oil that is commonly used in cosmetics. Mineral oil rarely causes adverse responses and does not solidify and clog skin pores. It is light and affordable, and it aids in reducing water loss and keeping the body hydrated. In the making of creams, a variety of mineral oils are used.

· Examples: Light liquid paraffin, Heavy liquid paraffin, Liquid petroleum.

· Vegetable oil forms a barrier on the surface of skin, slowing the loss of water and assisting in the maintenance of skin plumpness. Vegetable oils can also be used to creams or personal care products to thicken the lipid or oil part. Almond oil, germ oil, avocado oil, sunflower oil, and other similar oils are examples.

· Glyceride oil: Glyceride oil is mostly vegetable oils. Examples of glyceride oils are almond oil, arachis oil, castor oil, coconut oil, olive oil etc.

· Waxes: Beeswax, carnauba wax, ceresin, spermaceti, and other waxes are used in the formulation of cream. Waxes are utilised in cosmetics because they aid in the separation of oil and liquid components in emulsions. These waxes also thicken the lipid part of the skin and cause it to cling to the surface.

· Fats: Various fats are utilised in the production of creams. Animals, plants, and minerals can all provide these components. Glyceride oils and fats can come from either animals or plants. Depending on the technique utilised, they form soap or fatty acid and glycerin when saponified. Lauric, margaric, plamitic, stearic, and saturated fatty acids are the most frequent. Oleic acid is a liquid unsaturated fatty acid that is widely used. Olive oil, almond oil, sesame oil, peanut oil, coca butter fat, mutton tallow, lard, and beef stearine are among the most often used oils in various cosmetics.

· Lanolin: It's made from a sheep's wool fat. Lanolin is divided into two types: hydrous and non-hydrous. The hydrous lanolin contains between 25% and 30% water. The melting point of anhydrous lanolin is 38°C-42°C, and it has a mild odour. These chemicals work as lubricants on the skin's surface, making it appear soft and smooth. Lanolin aids in the formation of emulsions and mixes well with other ingredients in cosmetics and personal care products.

· Emollients: Emollients, generally known as moisturisers, are products that assist soften skin or treat dry skin. Mineral oil, squalene, and lanolin are some of the most common emollients. They function by enhancing the skin's ability to store water, coating it with an oil layer to prevent water loss, and lubricating it. Emollient is a moisturising substance that aids in the softening of skin or to treat dry skin. It lubricates the skin and helps it retain water.

· Colors: Colors were mostly derived from natural elements such as turmeric, saffron, and indigo prior to the emergence of modern technology. Colors were created in the laboratory after the nineteenth century with higher colouring intensity. They could also be made without the use of wild-harvested plants. Color is the element that gives the cream its appealing appearance. It can be obtained both naturally and synthetically in a laboratory setting.

· Humectants: These are crucial multi-functional components that may be found in almost all skin care products. Humectants are organic substances that have a high hydroscopicity. These are the materials that have the ability to absorb and hold water. These have numerous advantages, including moisturization, exfoliation, and so on. Glycerin, Hydroxyethyl urea, betaine, sodium PCA, Sodium-L-Lactate, and other humectants are examples. [5]

· Perfumes: It's used in a number of items to add a pleasant scent and disguise the odour of some substances. It's found in all kinds of cosmetics. Perfume is a substance that gives out a perfume or odour, such as a sweet and pleasant aroma. Natural scents that are utilised in creams include:

White Blossoms

Rosy Dreams

Orange Blossom

· Vitamins: Vitamins are necessary for the body's and skin's physiological functions to work properly. Vitamins A, B, C, E, and others are commonly utilised in cream composition.

· Preservatives: Preservatives are necessary in cosmetics to avoid changes induced by microorganisms and contamination throughout formulation, shipment, storage, and usage by consumers. Synthetic preservatives are excellent in preserving items when used in low concentrations. They exhibit a number of antibacterial and antifungal activities. Natural preservatives can be used in a wide range of pH levels, and customers prefer natural preservatives to synthetic preservatives^3,4,6,8,9,10.

Advantages of Cream as A Drug Delivery System:

1. It is the most convenient method of drug delivery.

2. It obviates the need for first-pass metabolism.

3. Cream is quite useful for rectal and vaginal medication administration.

4. It is non-intrusive in nature.

5. It results in high patient satisfaction.

6. Medication can be easily stopped as needed.

7. Gastrointestinal incompatibility is avoided.

8. It is a safe and effective method of delivering medication molecules with lower concentrations than traditional methods^2,6,8.

Disadvantages of Cream as A Drug Delivery System:

1. The medicine or excipients may cause skin irritation or dermatitis.

2. Most medications have a high molecular weight and are fat soluble, thus they cannot be absorbed through the skin or mucous membranes.

3. Absorption is extremely slow.

4. It can only be used for medications that require a very low plasma concentration to work².

Evaluation Parameteres of Creams:

1. Determination of pH: The pH can be determined at room temperature using a standard digital pH metre and an appropriate amount of the formulation diluted with a suitable solvent in a suitable beaker. A pH metre was used to monitor the pH, which was calibrated with standard buffer solutions at pH 4, 7, and 9 before each usage. At room temperature, the electrode was put into the sample 10 minutes before the reading was taken.

2. Physical appearance: The colour, roughness, and grade of the cream can all be used to determine its physical appearance. The appearance, colour, and scent of the compositions were all visually assessed.

3. Spreadability: When two slides are placed in between them under the direction of a given force, the time taken to slip off the gel is measured in seconds. The extra sample was sandwiched between the two glass slides, and a specific amount of weight was applied to the glass slides to compress them to a consistent thickness. A 70-gram was added, and the time it took to separate the two slides was recorded.

Spreabability was calculated using the formula

S = M.L / T

where,

M = wt tied to upper slide,

L = length of glass slides,

T = time taken to separate the slides.

4. Saponification value: 2gm of material was refluxed for 30 minutes with 25ml of 0.5 N alcoholic KOH, then 1ml of phenolphthalein was added and titrated with 0.5N HCl right away, noting the reading as 'a'. Rep the procedure, this time omitting the substance to be analysed. Take note of the 'b' reading.

Saponification value = (b-a)*28.05/w

Where,

w = weight of substance in gram.

5. Acid value: The substance is dissolved in an accurately weighed 50ml mixture of equal quantities of alcohol and solvent ether, the flask is attached to a reflux condenser, and the liquid is steadily heated until it reaches the desired temperature until the sample is completely dissolved, 1ml of phenolphthalein is added and titrated with 0.1N NaOH, until a faintly pink colour appears after 30 seconds of shaking.

Acid value = n*5.61/w

Where,

n = the no. of ml of 0.1 N KOH solution.

w = the weight of substance in gram.

6. Viscosity: A Brookfield Viscometer was used to test the viscosity of the compositions. The gels were rotated at three different speeds: 0.3, 0.6, and 1.5 revolutions per minute. The gel's viscosity was calculated by multiplying the matching dial reading by the factor specified in the Brookfield Viscometer catalogue.

7. Stability: Drug product stability testing begins with drug discovery and ends with the demise of the chemical or commercial product. Stability studies were carried out in accordance with ICH recommendations to test the drug and formulation stability. The stability tests were carried out in accordance with ICH recommendations. For three months, the cream was put into bottles and preserved in a humidity chamber at 402°C/75.5% RH. Samples were evaluated for physical characteristics, pH, and viscosity at the conclusion of the investigations.

8. Homogeneity: Visual appearance and touch were used to check for homogeneity in the formulation.

9. Removal: The ease with which the creams applied could be removed was tested by washing the applied region with tap water.

10. Dye test: The cream is combined with the scarlet dye. Put a drop of cream on a slide, cover it with a cover slip, than look at it under a microscope. It's an o/w type of cream if the dispersion globule is red and the ground is white, and a w/o type of cream if the disperse globule is white and the ground is red.

11. After feel: After applying a predetermined amount of cream, the emolliency, slipperiness, and amount of residue left were assessed.

12. Type of smear: The type of film or smear created on the skin after application of the cream was examined.

13. Irritancy study: On the left-hand dorsal surface, draw a 1sq.cm area. The cream was applied to the designated region, and the duration was recorded. Irritation, erythema, and edoema were assessed at regular intervals up to 24 hours and reported.

14. Accelerated stability study: Formulation undergoes an accelerated stability evaluation in accordance with ICH recommendations^{2.3.6.7.27.28.29}.

CONCLUSION:

Cream is the topical pharmaceutical preparation used for treating various skin related issues. It is mostly preferred due to its convenient properties as compared to other dosage form also it involves various advantages. Skin is the most accessible part of the body leading it to be widely accepted by the society. Creams as a topical dosage form will always be an interesting topical to deal with. There are still many areas related to cream which needs to be discovered or improvised in regards with the demand of patients.

REFERENCES:

1. Ashni V, Sukhdev S, Rupinder K, Upendra J. Topical gels as Drug delivery system: A review. Pharmaceutical Sciences Review and Research. Nov-Dec 2013; 23(2): 374-382.

2. Pratiksha R, Adarsh P, Sujit D. Pharmaceutical creams and their use in wound healing: A review. Journal of Drug Delivery and Therapeutics. 2019; 9(3-5): 907-912.

3. JamshiyaSahmsu. Formulation and evaluation of herbal skin cream for Wound Healing. 2017

4. AK Mohiuddin. Skin care creams: formulation and use. America Journal of of Dermatological Research and Reviews. 2019 2:8.

5. Tarun G, Goutam R, Amit G. Comparative review on additives of topical dosage forms for Drug Delivery. 2015; 22(8), 969-987, DOI: 10.3109/10717544.2013.879355.

6. Anchal S, Swarnima P, Arpita S, Siddique A, Nitish P. Creams: A topical drug delivery system (TDDS). Europen Journal of Pharmaceutical and Medical Research. 2021; 8(1): 340-342.

7. Lalita C, Shalini G. Creams: A review on classification, preparation methods, Evaluation and its application. Journal of Drug Delivery and Therapeutic. 2020; 10(5-5): 281-289.

8. Tanesh S, Trun P, Sagar S, Bina G. Skin cream as topical drug delivery system. Journal of Pharmaceutical and Biological Sciences 2016; 4(5): 149-154.

9. James Q, Del R, Jacquelyn L. Skin structure and function: Translation of Research to Patient Care. 2011; 4(9): 22-42.

10. Mohiuddin AK. Cosmetics in use: A pharmacological review. Journal of Dermatology and Cosmetology. 2019; 3(2) : 50-67.

11. Hagar L, Labiba EI-K, Tobias K and Marc S. Mechanism and determinants of nanoparticles through human skin. 2011; 3:4989-499, DOI: 10.1039/clnr11109d.

12. Pinaki D, Ram P, Mandip S. Interaction of nanoparticles and cell penerality peptides with skin for transdermal drug delivery. 2010; 27(7): 247-259, DOI: 10.3109/09687688.2010.522203.

13. Mahdi R, Elise L, Samuel B, Davide B. A snapshot of transdermal and topical drug delivery research in Canada. 2019; 11:256. DOI: 10.3390/ Pharmaceutics11060256.

14. Larissa P, Dominique L. Film forming systems for dermal drug delivery. 2021; 13: 932.

15. Benedetta S, Ivan Z, Roberta M et al. Cream formulation impact on topical administration of engineered colloidal nanoparticles. 2015: 1-14, DOI: 10.1371/journal.phone.0126366.

16. Ashish A, Mohini K, Abhiram R. Prepartion and evaluatin of polyherbal cosmetic cream. 2013; 5(1): 83-88.

17. Sameeha K, Shalaka A, Ashwin K, Ashwini G. A mini review- Pharmaceutical creams. 2021; 10(4): 60-62. DOI: 10.36347/SAJP.2021.V10i04.001.

18. Vinod S, Kris D, Gary E ,et al. Topical and transdermal products. 2009; 35(3): 750-764.

19. Tais G, Ulrich S, Lihong J, Mingyann G, et al. Penetration of quantum dot particles through human skin. 2010; 6: 586-595.

20. James Q, Del R. The role of skin care and maintaining proper barrier function in the management of Rosacea. 2007; 20(8): 485-489

21. Ahmad O, A del M, Ali M, Mohammad T. Topical application of aloevera accelerated wound healing, modeling and remoulding. 2016; 77(1): 37-46.

22. Susan Wijnhoven. Interaction of inorganic nanoparticles with the skin barrier. National Instuite for Public Health and the Environment. 2-42.

23. Dr. M.S Darade, Dr. S. Muthukumar, Dr. M.S. Kadam, Mr. R. Shrivastava; Research & development in pharmaceutical science; Bhumi Publishing; 1st Edition 2021.

24. Saima j, Sabiha K, Muhammad, et al. Anti ageing potential of phytoextrect loaded pjarmaceiutical creams for human skin cell longetivity. 2015;2-17, DOI: 101155/2015/709628.

25. Z.D Draelos, L.A Thamen; Cosmetic formulation of skin care Products; Taylor & Francis group.

26. Christian S, Nina D, Jan K. Skin care product for healthy and diseased skin. 2018; 54: 183-200. DOI: 101159/000489532.

27. Ashish D, Amit U, Naveen S, Ravish S et al. Optimization of formulation and process parameter and product evaluation of Galatomannan- Borate complex based cream. Research Journal of Pharmaceutical Dosage Form and Technology. 2009; 1(3): 229-232.

28. Vani M, Mounika K, Vamsi T, Praneetha K, et al. Formulation phytochemical, physical, biological evaluation of polyherbal vanishing cream and facewash. Research Journal of Pharmaceutical Dosage Form and Technology. 2020; 12(3): 139-149. DOI: 10.5958/0975-4377.2020.00024.5

29. Shikha A, Yogesh S. Formulation and evaluation of herbal cream containing extract of Ziziphus jujube leaves for analgesic potential. Research Journal of pharmaceutical Dosage Forms and Technology. 2012; 4(6): 320-323.

Received on 23.03.2022 Accepted on 25.04.2022

Research J. Topical and Cosmetic Sci. 2022; 13(1):35-43.

DOI: 10.52711/2321-5844.2022.00006