THE SKIN MOISTURIZING EFFECTS OF DIFFERENT CONCENTRATIONS OF UREA: A CLINICAL AND CORNEOMETRY STUDY*

Abstract

Objectives: The objective of this study was to evaluate the effects of different concentrations of urea on skin moisture.
Institution: A double blind, randomized, placebo-controlled study was conducted at the Medcin Instituto da Pele – Clinical Research Center –, in Osasco, SP, Brazil.
Material and methods: Individuals with dry skin were submitted to one application of three different concentrations of a urea moisturizer, namely 3%, 5%, and 10%, and a control moisturizer. Clinical, subjective, and corneometry measurements were evaluated at 1, 4, and 6 hours.
Results: All moisturizers, including the control emulsion, improved significantly the skin moisture in the first evaluation (p < 0.05); 10% urea was superior to other concentrations, especially at the 4-hour evaluation, when it was compared with 3% urea, and at the 6-hour evaluation, when compared with the 5% and 3% presentations; at the 1-hour evaluation, patients referred itching and stinging with the use of 10% urea moisturizer.
Conclusion: The duration of the hygroscopic properties of urea is directly related with its concentration. Adverse symptoms, such as stinging, were observed only with higher concentrations.

Keywords: UREA

INTRODUCTION

Dry skin is frequently seen in several skin disorders, such as atopic eczema, ichthyosis, and contact dermatitis. The reduction in the water content of the epidermis changes the properties of the skin barrier, favoring the penetration of xenobiotics, besides reducing the itching threshold and predisposing to skin infections.¹

The use of formulations containing oils and hygroscopic elements favors the recovery of the barrier and maintenance of adequate moisturizing levels. Its effects are felt immediately after the application, with improvement of the common signs of dry skin, like roughness and desquamation.²

Urea is a moisturizing agent widely used for its capacity to retain water in the epidermal layer (hygroscopy); its natural presence in the corneal layer, representing 7% of the Natural Moisturizing Factor, has been demonstrated in the literature.³ For topical use, its moisturizing action is associated with the concentration used and the excipient it is incorporated into.

According to the results of an experimental study consisting of the application of lauryl sulphate on skin pre-treated with urea-containing moisturizers, the improvement of the skin barrier produced by urea also seems to prevent irritations.^4,5

Topical urea can also increase the absorption of other agents that are associated with it in the same preparation.^6,7,8 This effect can be partly responsible for the irritation described.⁹

In moisturizers, urea is available in the market in different concentrations, whose predominant excipient is an emulsion. The studies of Wohlrab¹⁰ demonstrated significantly higher concentrations of urea in the corneal layer when using the 10%-concentration than with the 2- or 5%-concentration.

The moisturizing and skin barrier restoring effects of urea are well known, but the correlation between efficacy and concentration has not been extensively studied.

OBJECTIVE

The objective of this study is to evaluate the clinical and instrumental impact of the concentration of topical urea on moisturizing the skin after a single application in individuals with dry skin.

MATERIAL AND METHODS

Type of study
This is a prospective, double-blind, randomized, placebo-controlled study.

Study population
Twenty adult patients of both genders (15 women and 05 men), complaining of dry skin in the upper limbs, participated in this study. All patients were examined by a dermatologist to determine the clinical presence of xerosis.

Study site
This study was conducted at a private clinical research center – Medcin Instituto da Pele, in Osasco, São Paulo, Brazil.

Methodology
After the clinical confirmation of xerosis, patients were oriented to avoid applying any products on the forearms for the 4 following hours, and were asked to return to the department for measurement of the skin moisture.

A Corneometer® (Kourage & Khazaka) was used to measure the level of skin moisture, expressed in corneometry units and based on capacitance, in four predetermined 2-cm² areas on the anterior face of both forearms (Figure 1).

After recording the data of all four areas, they were randomly assigned to receive the same amount (0.2 mL) of four formulations: 10% urea in standard excipient; 5% urea in standard excipient; 3% urea in standard excipient; and the standard excipient without urea. The products were uniformly spread in each area 6 to collect the data at four different moments: initial, 1 hour, 4 hours, and 6 hours after the application. All patients remained in a room with standardized temperature and humidity during the study period.

The following parameters were evaluated: clinical improvement of dry skin (classified as improved or not improved), presence of itching, stinging, and pruritus, and duration of the level of moisture.

Ethical aspects
This study was approved by the Ethics on Research Committee and designed according to good clinical practices. All patients signed an informed consent before participating in the evaluations.

RESULTS

Clinical efficacy and adverse events

All individuals completed the study without visible adverse reactions on anyone of the four areas evaluated. Clinical evaluation of the dry skin showed improvement at all times with the urea-containing creams, but it did not show any improvement 4 and 6 hours after application of the control cream.

Two out of 20 patients complained of itching and mild stinging 1 hour after the application of the 10% urea cream. However, those patients had no complaints at the 4-hour evaluation.

Instrumental efficacy evaluation
The group presented a mean corneometry of 35.08 corneometry units. The T test was used for the statistical evaluation of the data.

One-hour evaluation
In the first hour after the application, significant differences were not seen in the moisturizing effects among the different concentrations of urea, but for the comparison between the control cream and the 5- and 10%-concentrations (Table 1).

Four-hour evaluation
The moisturizing effects were greater for the higher concentrations; a significant difference was seen between the 10- and 3%-concentrations; a difference was not seen between the 3%-concentration and the control cream (Table 2).

Six-hour evaluation
Differences among concentrations can be seen, demonstrating the superiority of the 10%-concentration over the 3- and 5%-concentrations; 3% urea also showed a significant superiority over the control cream (Table 3).

Duration of the moisturizing effect
The moisturizing effects stabilized after 1 hour for the 3% cream, decreasing from the 4th hour on; the 5% urea cream maintained increased levels of moisture, with only a slight reduction between 4 and 6 hours; the 10%-concentration showed better moisturizing response, which continued up to 6 hours (Table 4).

The duration and intensity of the moisturizing effect are greater for 10% urea, which becomes evident at the 6-hour evaluation (Chart 1).

Evaluating the corneometry measurements of urea-containing creams, a positive correlation is seen between the concentration and the moisturizing effect, which is more significant for the duration than the intensity of the effect; the difference in efficacy increases, becoming progressively significant with time, which demonstrates that the duration of the moisturizing effect depends on the concentration of urea.

DISCUSSION

The moisturizing capacity of urea has been well-documented in dermatology; its efficacy for topical use has been described by several authors and in different conditions that cause dry skin, both physiological (aging) and pathological (atopic dermatitis, contact dermatitis, psoriasis, ichthyosis, etc.).
Its secondary action of increasing the moisture in the corneal layer, measured by epidermal impedance (corneometry), was demonstrated by Lóden in atopic patients¹², as well as by Kuster et al. in children with ichthyosis vulgaris¹³. The moisturizing effects of urea-containing formulations have also been compared with other active moisturizers; using corneometry measurements, Lóden compared the moisturizing effects of three formulations containing glycerin, glycerin and polyvinylpirrolidone acid, and urea, which demonstrated similar capacity¹⁴.
The excipient also influences the moisturizing efficacy of urea, as demonstrated by Couteau et al., comparing different formulations with the same concentration of urea¹⁵. Similarly, the keratolytic effect, detectable with 20%-concentrations, is stronger in petrolatum-based occlusive preparations¹⁶; therefore, the excipient used in the present study was similar in all creams, and the concentration of urea was the only variable.
In this study, all individuals complained of dry skin at the application site, which was confirmed both clinical and instrumentally; the clinical improvement seen in all areas, including that of the control cream, can be explained by the immediate improvement in texture caused by an emulsion. The difference was seen in the duration of the effect, which increased with the higher concentration of urea.
Serup conducted studies comparing formulations with different concentrations of urea in individuals with dry skin:
In one of the studies, the comparison of two concentrations (3 and 10%)¹⁷ did not show statistically significant differences in moisture, measured by corneometry, after three weeks; similarly, both concentrations had positive evaluation regarding skin desquamation and dryness. However, only the 10% formula influenced significantly the transepidermal water loss.
In another study comparing the efficacy of a single application¹⁸, a model similar to ours, Serup found significant differences between the 3% and 10% urea after 3 hours.
The data of the present study demonstrated that the differences increase with time and the 10%-concentration has a longer-lasting effect.
Although transitory burning sensation and pruritus have been reported in patients with atopic dermatitis treated with topical urea¹⁹, it is frequently used due to the improvement of signs like erythema and pruritus, as well as an increase in the moisture of the corneal barrier with the continuous use²⁰.
In the present study, the discomfort is transitory and seems to be related with a higher concentration of urea. In a similar study²¹ comparing 4% urea and glycerin, the latter was better tolerated, although the incidence of pruritus and burning was not statistically significant.
In our study, those symptoms were associated only with the higher concentration (10%), suggesting that the irritation is dose-dependent.
The data of this study demonstrated the impact of different concentrations of urea in the retention of water by the corneal layer. This effect, measured after a single application indicates the lack of a linear and proportional correlation between the concentration used and the moisturizing activity.

CONCLUSION

Urea has a significant moisturizing action in all concentrations evaluated, which lasted for up to 6 hours with a single application; however, the intensity and duration of this effect are related with the concentration used. The moisturizing effect was longer-lasting with 10% urea.

Symptoms related with irritation (stinging, itching, pruritus) were seen with the 10%-concentration, suggesting that the irritation can be reduced by simply decreasing its concentration; on the other hand, to maintain significant levels of moisture over time, lower concentrations of urea should be applied more often.

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