2. Methods of Preparation
Moisturizers can be categorized into oil in water (
o/
w) moisturizers and water in oil (
w/
o) moisturizers based on the nature of the dispersed phase [
129]. Compared to ointments, water in oil (
w/
o) is less greasy and has better spreadability, while oil in water (
o/
w) readily rubs into the skin and is easily removed by water (
Table 1) [
130].
Table 1. Different dispensing formulations of moisturizers.
2.1. Preparation of Oil in Water (o/w) Moisturizer
The emulsifier and oil-soluble components are combined in a beaker and melted at 75 °C in a water bath. Water, water-soluble materials and preservatives are melted at 75 °C in another beaker. The oil phase is placed in a mortar and pestle after heating, and the water phase is gradually added and triturated until a clicking sound is heard. Finally, perfuming agents and/or preservatives are added as the temperature cools down. The amount of water in this preparation will be greater than the amount of oil [
70].
2.2. Preparation of Water in Oil (w/o) Moisturizer
The emulsifier and oil soluble components are melted together at 75 °C in one beaker. Water and water-soluble materials are taken to another beaker and melted at 75 °C. The water phase is placed in a mortar and pestle after melting, and the oil phase is gradually added and triturated until a clicking sound can be heard. The perfuming agent is added after the cream has cooled to the desired temperature. This preparation would have a lower amount of water phase and a higher amount of oil phase [
70].
Depending on the dispensing medium, moisturizers come in a variety of formulations. A cosmetic emulsion is the most common delivery method. The emulsification method incorporates several steps that contain the active ingredients (
Table 4) [
6].
3. Characterization
3.1. Determination of pH
At room temperature, the pH of the cream can be determined using a standard digital pH meter by diluting an appropriate quantity of the formulation with a suitable solvent in a beaker [
70]. However, it is advisable to calibrate the pH meter before use with a standard buffer solution at pH 4 and pH 7 [
133,
134]. Meanwhile, according to Maha et al. (2018), the pH of a topical preparation should be between 4.5 to 6.5, which corresponds to the pH of the skin. The pH should not be too acidic, as this can irritate the skin, nor should it be too alkaline [
135].
3.2. Organoleptic Properties/Physical Appearance
Involves grading of its texture and color [
70]. To be more precise, the clarity, smell, texture, and foreign particles present were evaluated. The grittiness and stickiness were determined by rubbing them between two fingers [
136]. Esoje et al. (2016) suggested that this test was to be conducted randomly, at different temperatures and storage duration to observe for any changes [
137].
3.3. Centrifugation Test
It is conducted to assess the chemical and physical stability of the formulation under the influence of centrifugal force [
138,
139]. Five to ten grams of sample were centrifuged at 3000 rpm for 30 min at room temperature. The formulation was examined for phase separation after the centrifugation process, which is an indicator of formulation instability [
109,
138,
139]. Meanwhile, Fernandes et al. (2018) evaluated both organoleptic (look, color, feel, thickness) and physical (phase separation and creaming) properties. Phase separation is denoted by the presence of caking, coalescence, and flocculation [
140].
3.4. Mechanical Vibration Test
This test assesses the formulation’s stability when subjected to mechanical vibration, which can result in phase separation and indicate instability. Five grams of sample were vibrated for 10 s on a vortex shaker (Haidalph) [
109].
3.5. Spreadability
Spreadability is a term used to describe the area a topical application spreads after being applied to the skin of the affected areas, with shorter intervals indicating better spreadability [
141]. Between two glass slides, the formula was applied and pressed to achieve a uniform film thickness. Following that, a weight of 10 g was added to the pan, and the top plate was pulled using a string attached to a hook. The time it takes for the upper glass slide to travel 10 cm over the lower plate is recorded, and the spreadability (S) is calculated using the formula [
142].
3.6. Saponification Value
The saponification value is a measure of saturation, with higher values indicating shorter chain fatty acids in the glycerol bond [
143]. Meanwhile, Saraf et al. (2011) stated that the saponification value is a measurement of the amount of free fatty acid esters in a sample which affects the formulation’s stability, pH, and cleaning properties. The formulation’s saponification value should be appropriate; if the fat content is too high, it can contain too much fatty acid, which is susceptible to hydrolysis and may lead to rancidification and microbial growth [
144]. Two grams of substance were refluxed for 30 min with 25 mL of 0.5 N alcoholic KOH; then, 1 mL of phenolphthalein was applied and titrated with 0.5 N HCl right away, marking the result as ‘a’. The procedure was repeated, this time omitting the material to be tested, marking the result as ‘b’ in the reading [
70].
3.7. Density
This is the proportion of a substance’s mass to the volume it takes up. This parameter is an indication of air incorporation or the loss of volatile ingredients in liquids or semi-solids. A graduated cylinder and a balance were used to determine the (apparent) density of the formulations. The test was performed in triplicate with 10 mL of each formulation, and an average was determined. The apparent density is correlated with the recipient’s capacity [
109].
3.8. Light Test
The formulations were placed in clear plastic containers and exposed to intense light for 15 days using a daylight bulb with a photoperiodicity system consisting of 16 h of light and 8 h of dark. The samples were analyzed for any changes in physical properties, such as clarity, appearance, or color, as well as liquefaction, at the end of the exposure period. Any visible phase separation or color change is an indication of product instability [
109].
3.9. Acid Value
The acid value is a measurement of the amount of free acid in fats or oils that causes rancidity upon exposure to heat or light [
145]; 10 g of substance was dissolved in a precisely weighted 50 mL mixture of equal parts alcohol and solvent ether. The flask was attached to a reflux condenser and slowly heated until the sample was fully dissolved; 1 mL of phenolphthalein was added and titrated with 0.1 N NaOH until the appearance of a slightly pink color after 30 s of shaking [
70].
3.10. Viscosity
The viscosity is used to evaluate the formulation’s stability with regard to consistency and as a result, to predict how the substance will behave over time [
109]. The Brookfield Viscometer can be used to calculate the viscosity of formulated creams [
70]. Viscosity values are calculated by multiplying the dial reading with correction factors in the Brookfield viscometer. Increased viscosity during storage indicates kinetically unstable emulsions, in which free-moving droplets collide and appear to coalesce [
135].
3.11. Homogeneity
Shows the distribution of materials in the formula [
135]. Touch and visual appearance were used to check for homogeneity [
70]. The homogeneity of cream can be assessed by smearing 50 mg of preparations onto a clean object-glass, showing a homogeneous arrangement with no clear grain observation [
135]. Homogeneity and texture were conducted simultaneously by Chen et al. (2016) by pressing a small amount of the formulation between the thumb and index finger to assess the presence of coarse particles. The immediate skin feel was also assessed, which includes stiffness, grittiness, and greasiness [
146].
3.12. Dye Test
To determine the type of emulsion [
133]. A drop of cream was placed on a slide after the cream was mixed with scarlet dye. Then, the slide was covered with a coverslip and examined under a microscope;
o/
w creams have dispersed globules that appear red and the ground is colorless and vice versa for
w/
o creams [
70].
3.13. After Feeling Test
After application of a fixed amount of cream, the slipperiness, emollience and residue left were assessed [
70].
3.14. Type of Smear
The smear pattern developed on the skin after the cream application was assessed [
70].
3.15. Irritancy Study
This test determines the characteristics of produced formulations in terms of skin irritation [
147]. On the left-hand dorsal surface, draw a 1 sq.cm section. The cream was applied to the designated location, and the duration was recorded. Erythema, irritation and edema were assessed and recorded at regular intervals for up to 24 h [
70]. Another type of skin irritation test was conducted using albino rabbits. During the test time, these animals were held in separate cages and given fresh food and water; 24 h before the test, the fur on the neck and thighs was shaved to reveal a sufficiently wide test area. Surgical spirit was used to disinfect the test site briefly. The test area was then covered with cream. For 24 h, 48 h, and 72 h after application, the test site was monitored for erythema and edema [
141]. Irritancy studies should be performed on animals prior to human studies. Once the prepared formulation demonstrated high compliance in animal tests, then it could be applied to healthy human volunteers to determine its safety for topical use [
148]. Both animal and human studies are preferably conducted in skin irritancy tests as some substances are harmful to rabbits but not to humans, and vice versa [
148,
149].
3.16. Spectrophotometric Test
It is another form of stability testing involving the dilution of formulations in ultra-pure water at a ratio of 1/100 (
m/
v); then they are analyzed using spectrophotometry in the UV-VIS region (210 nm to 600 nm), with the spectrum compared to the control formulation’s reference spectrum. Formulation instability is described as variations in intensity or absorption bands’ wavelength. This indicates that some changes have occurred in the color intensity or even modification of the coloring content [
109].
3.17. Microbial Stability
The microbial contamination test was used to assess the formulations’ microbial stability. After preparing the bacteria and yeast culture medium, it was autoclaved for 20 min at 125 °C, and then 20 mL of the culture medium was poured into a sterile Petri dish. The Petri dishes were then inoculated with 0.2 g of each formulation in the center of each plate, and incubated for 3 days at 37 °C or 25 °C, depending on the inoculated microorganisms. Plates were removed after the incubation period and tested for microbial growth, which indicates contamination [
109].
3.18. In Vitro Occlusivity Test
The occlusion factor was used to assess the formulations’ occlusivity. When the occlusion factor is zero (“0”), there is no occlusion effect when compared to the reference; “100” is the highest occlusion factor, indicating complete surface coverage by the topical formulation [
150,
151]. Creams with a higher occlusion effect result in more moist skin that is more pliable and maintains its moisturizing effect [
151]. Each beaker with a height of 4.6 cm and a diameter of 3.2 cm was filled with 10 g of distilled water. Then, the open end was covered with Whatman filter paper (0.45 pore size) on which 200 mg of the sample was uniformly distributed. After that, the beakers were set at 37 ± 2 °C/607 ± 5% RH for 48 h. The in vitro occlusivity of all formulations, prototype formulations, and the negative control in which the filter paper was left uncovered were investigated to determine the water flux. The occlusion factor F was determined as follows [
152]:
where
A = Water flux via uncovered filter (percent water loss) and
B = Water flux via filter when covered by test preparation (percent water loss).
3.19. Accelerated Stability Study
According to ICH guidelines, all formulations were subjected to accelerated stability testing for a duration of 2 weeks at a temperature of 25 ± 2 °C and 40 ° ± 2 °C, with two relative humidity conditions, specifically 60 ± 5% RH and 75 ± 5% RH. The cosmetic formulations were examined for organoleptic characteristics (texture, smell, color, phase separation and consistency) and their pH value was determined after 8 days. At the end of the storage period, the process was repeated [
70,
109].
3.20. Preference Test
Color, scent and skin sensation were the criteria of preference tests focused on sensory assessment. A numerical scale was used to determine the degree of preference as based on the
Table 5 [
142]:
Table 2. Different dispensing formulations of moisturizers.
4. Uses and Applications
Moisturizers are beneficial for a variety of purposes. There is evidence of biological effects that support the use of moisturizers in medicine [
118]. Many moisturizers block cyclooxygenase activity, which inhibits the development of proinflammatory proteinoids, and thus have a calming effect on inflamed skin, leading to their anti-inflammatory action. Mineral oil-based moisturizers have a low-level antimitotic effect on the epidermis, making them effective in inflammatory dermatoses, such as psoriasis, which have increased epidermal mitotic activity. Emollients reduce itching by inhibiting the development of cytokines. In addition, the cooling effect of water evaporating from the skin surface after using water-based moisturizers contributes to the antipruritic effect. Sunscreens with varying sun protection factors are also used in moisturizers, offering extra sun protection (photoprotective action). Moisturizers also have antimicrobial and wound-healing properties [
6].
Skin hydration, friction, scaling, and mechanical properties are all affected by moisturizers. A series of changes occur after a single application of a moisturizer, all of which reflects the moisturizer’s composition. Initial changes tend to be related to the moisturizer’s water content, which includes increased evaporation from the skin surface, decreased temperature, and skin softening. Changes occur with repeated applications over time, which are assumed to be caused by the moisturizer’s lipid phase, involving a reduction in scaling, increased hydration and discrete color changes. Specific additives, such as urea, alpha-hydroxy acids, or glycerol, may help to reinforce some of these improvements [
118].
Moisturizers are often prescribed as preventative measures and adjunct therapy for a variety of dermatological conditions. Moisturizers seem to be able to reverse some of the barrier defects seen in conditions, such as atopic dermatitis, allowing for improved disease control. Moisturizers have been studied for their adjuvant properties. The use of a moisturizer as an alternative to active corticosteroid treatment of the skin has been shown to minimize the quantity of corticosteroids required, without compromising treatment efficacy. It is postulated that the moisturizer’s lipid content may play a role, but the mechanism underlying this remains unclear [
118].
There is also a possibility that applying a moisturizer meets an atavistic psychological desire for physical contact, which is reinforced by the moisturizer’s immediate physical impact. Using a moisturizer necessitates extensive touching, either by oneself or by another person, resulting in enhanced sensory perception. It is also likely that additional psychological factors may be overlooked when moisturizers are used, such as stress coping and a sense of security, thus reinforcing the use of moisturizers [
118].
Moisturizers are often advertised and, as a result, are able to generate significant revenue for all advertising companies. While emolliency is an essential feature of moisturization, advertisement has almost fully replaced the conventional definition of creams or emollients. Marketing concepts promote that skin that is dry and dull is unattractive, while young and attractive skin is supple and moist. Moisture is needed for dry skin, which obviously can be compensated by the usage of moisturizers. Although there is no sufficient evidence of a sex disparity in dryness parameters, the strong focus on this chain of reasoning has persuaded a large number of women that their skin is dry, further promoting the expanded use of moisturizers [
118].