50 Basic Topical Therapy with Emollients
in Atopic Eczema
W. Gehring
50.1
Introduction
Topical therapy in atopic eczema has to consider par- ticularly sensitive skin due to the disturbed epidermal barrier function; this disorder most likely occurs through qualitative and quantitative alterations in epi- dermal lipids [3, 15], which leads to a deficit in stratum corneum hydration [21] and in consequence to reduced epidermal barrier function with increased transepidermal water loss. The ultimate role of any topical basic therapy is the improvement of stratum corneum moisture and stabilization of the reduced epi- dermal barrier function.
50.1.1
Vehicle Systems
Topical vehicles can be classified into lipophilic, amphi- philic, and hydrophilic systems, which again can be sub- classified according to specific characteristics [20].
50.1.2
Lipophilic Systems
Lipophilic systems can generally be mixed with lipids, but not with water.
Water-free systems are extremely fat, cannot be removed by water, do not bind to a moist basis, and
Lipophilic systems Water-free systems Apolar systems Polar systems Water-containing systems
Unstable water in oil emulsions Stable water in oil systems
show strong occlusive properties on the skin. Thus they act in a pro-inflammatory manner, increase heat sensa- tions, and have been effective as skin protection against hydrophilic irritants. Their use in exudative skin lesions, in intertriginous areas, on the scalp, or on moist surfaces is contraindicated.
Apolar systems are thick mineral oils or silicon oils or semisolid carbogels. Their galenics are stable, but not well adapted to the skin. They have extremely occlusive properties and may induce acanthosis and comedos.
Polar systems include fatty oils (medium- and long- chain unsaturated or brunched fatty acids), lipogels (triglyceride gels) and oleogels (hydrophobic gels).
They have less occlusive properties and are better toler- ated on the skin than apolar systems. Auto-oxidation, however, can lead to irritation.
These systems are biphasic consisting of lipids and water with lipophilic substances in the external phase and good stability on the skin.
Unstable water in oil systems, also called quasi- emulsions, cold cream, or pseudo-emulsions are emul- sions without emulgators, which often disintegrate on
Prescription example for polar vehicles Quantity (g) Unguentum molle
Lanolin 50.0
Petrolatum 50.0
Wool wax alcohol 6.0
White petrolatum 50.0
Solid paraffin 12.0
Liquid paraffin 32.0
White almond oil (lipogel)
Zinc oxide 5.0
Cera alba 5.0
Thin liquid paraffin 5.0
Almond oil 75.0
Prescription example Quantity (g) Unguentum leniens (cooling ointment)
Cera flava 7.0
Cetylpalmitate 8.0
Peanut oil 60.0
Water 25.0
the skin surface through warming or mechanical forces. They have a cooling and hydrating effect on the skin.
Stable water in oil systems can be subdivided into thick liquid or semisolid emulsions. They are able to take up water, can be easily distributed on the skin sur- face, and have mostly satisfactory cosmetic acceptance.
Stabile water in oil emulsions consist of three phases [17, 18]:
) External fatty phase
) Stabilized water droplets through mixed emulgator systems
) Containing crystals of emulsifiers
In the external fatty phase, there are two distinguish- able phases: a lipophil gel phase and a lipophil liquid phase. Similarly to petrolatum, the lipophil gel skele- ton is responsible for the consistency and structure
Prescription examples Quantity (g)
Lipophilic cream
Triglyceroldiisosterearate 3.00
Isopropylpalmitate 2.40
Hydrophobic basis gel 24.6
Potassium sorbate 0.14
Water-free citric acid 0.07
Magnesium sulfate-heptahydrate 0.50
Glycerol 85 % 5.00
Aqua purificata 64.29
Water in oil emulsion – water-rich
Urea 5.0
Glycerol 85 % 10.0
Triclosan 3.0
Eucerinum W/O vehicle (Beiersdorf, Hamburg) 82.0 Water in oil emulsion – water-rich
Urea 5.0
Glycerol 85 % 10.0
Triclosan 3.0
Evening primrose oil 15.0
Pioneer KWH Pharm 23.8
Acidum citric anhydricum 0.055
Magnesiumsulfate-heptahydrate 0.4
Aqua purificata Ad 100.0
of the preparation. Water/oil emulsion can substitute fat components in the stratum corneum, which may differ considerably from the physiologic barrier lipids. Through the water content of the internal phase and the occlusive effect they improve the hydration of the stratum corneum. Consequently, they are well accepted as vehicle in the treatment of atopic eczema.
However, a water content of at least 50 % should be given.
50.2
Amphiphilic Systems
Amphiphilic systems can be divided into water in oil (W/O) and oil in water (O/W) emulsions.
W/O emulsions are characterized by a high content of emulsifiers of the W/O type (HLB value < 10) and can be mixed with almost all lipids. The capacity to take up water is moderate to good. With water stable W/O systems are formed. Since they are not hydropho- bic, they can also be used on moist skin. A disadvan- tage is the common incompatibility with surface active substances.
O/W emulsions are characterized by a high content of emulsifiers (HLB value > 10). They can easily be mixed with water and also to a certain extent with lipids. They can easily be washed off and can be used in hairy areas. Their capacity to adhere to a moist surface is good and there is not much occlusive effect. Only occasionally do they have occlusive effects, but they can be washed off easily, do not cause heat sensations, are nonexudative, and do not lead to retention of secre- tions. They perform well as a vehicle in intertriginous areas.
The basic cream DAC (German Pharmacopeia) is an excellent example of an amphiphilic system with three phases [17]:
) Partly swollen gel skeleton of polyethylene glycer- olmonostearate and cetyl alcohol
) Totally “swollen” gel skeleton made out of glycerol- monostearate
) Coherent lipophilic phase
When water is added, the gel skeleton of polyethylene glycerolmonostearate and cetyl alcohol shows further swelling. Depending on the water content, the external phase is either hydrophilic or lipophilic. When there is a high water content, the system is similar to an O/W 464 50 Basic Topical Therapy with Emollients in Atopic Eczema
Prescription Example Quantity (g) Basic cream DAC
Glycerolmonostearate 4.0
Cetyl alcohol 6.0
Medium-chain triglyceride 7.5
White petrolatum 25.5
Macrogol-100-glycerolmonostearate 7.5
Propylenglycol 10.0
Water 40.0
emulsion. After application to the skin and evapora- tion of the bulk water, the system resembles a W/O emulsion.
50.3
Hydrophilic Systems
Hydrophilic emulsions can be divided into water-free or water-containing systems.
Water-free systems are polyethylene glycol gels.
They are generally semisolid and can be mixed with water depending on molecular size. They are not solv- able in lipids. On the skin, they give a fatty appearance without increasing the lipid content. They can be well distributed and easily washed off. There is no occlusive effect. In the presence of wound secretions they have osmotic activity. They are preferably used in hairy skin areas.
Water-containing systems can be further subclassi- fied into O/W systems, hydrogels, and cutaneous sus- pensions (shaking lotions). The water content is high, they can be mixed with water but only to a small extent with lipids. In acute inflammatory and moist skin lesions, cutaneous suspensions are indicated, as is the case for intertriginous areas.
Hydrogels have a strong exsiccating effect, but cool especially when they contain alcohol. Apart from their use in acute and subacute inflammations, they can be used in seborrhoic skin types and are commonly used for transcutaneous preparations.
O/W emulsions are widely used in dermatological topicals as well as in cosmetics. O/W emulsions seem to
Prescription Example Quantity (g)
Polyethylene glycols DAB
Polyethylenglycol 300 50.0
Polyethylenglycol 1,500 50.0
be complex systems. Their properties can be described, according to Junginger, with respect to their crystalline or liquid gel structure [16]. Five phases are distin- guished:
) Mixed crystals of O/W emulsifiers and W/O emulsifiers
) Interlamellar bound water
) Lipophilic gel phase with W/O emulsifiers ) Bulk water
) Dispersed lipophilic phase
The bulk water evaporates on the skin, rapidly leading to a cooling sensation. Due to the small concentration of the lipophilic disperse phase, there is little fattening effect. The marked hydrating influence results from the lamellar bound water. In our investigations with vari- ous O/W emulsions, we could not find a skin protective effect against tensides. This and the low fatty effect make O/W emulsions less acceptable in the treatment of atopic eczema, whereas they can be used in normal or seborrhoic skin.
A major disadvantage of O/W emulsions is frequent incompatibility, which must be considered, especially with magistral prescriptions.
Prescription Examples Quantity (g)
Hydrophilic emulsion vehicle
Sorbitanmonostearate 2.0
Macrogolstearate 3.0
Glycerol 85 % 5.0
Medium-chain triglycerides 5.0
Water-free citric acid 0.07
Potassium sorbate 0.14
Aqua purificata Ad 100.0
Nonionic hydrophilic cream
Isocetyllaurate/mystristate 10.0
Nonionic emulsifying alcohols 21.0
Glycerol 85 % 5.0
Potassium sorbate 0.14
Water-free citric acid 0.07
Aqua purificata Ad 100.0
Anionic hydrophilic cream
Isocetyllaurate/myristate 10.0
Emulsifying cetylstearyl alcohol type A 21.0
Potassium sorbate 0.14
Water-free citric acid 0.07
Aqua purificata Ad 100.0
50.4
Desired Vehicle Effects: Hydration of the Stratum Corneum and Induction of a
Diffusion Barrier Against Hydrophilic Irritants
The use of emulsions leads to an improvement of skin hydration, irrespective of the type of emulsion system.
The water content is critical. However, when washing, active irritants act on the skin (e.g., sodium lauryl sul- fate); only pretreatment with W/O emulsion was effec- tive in skin protection [1]. Pretreatment with an O/W emulsion did not show a protective effect. Therefore, we recommend a W/O system as skin protective emol- lients in patients with sensitive skin. This plays a major role in the management of patients with atopic eczema [8]. A general recommendation, however, is limited by the fact that many W/O systems have a low cosmetic acceptance.
50.5
Modulation of Vehicle Effects by Glycerol or Urea
In the treatment of atopic eczema, moisturizers have great importance: both urea and glycerol are able to improve stratum corneum hydration [1]. An increase in urea contents from 5 % to 10 % did not show further advantage. Therefore we recommend lower urea con- centrations in the treatment of atopic eczema in order to prevent incompatibility sensations. However, the degree of hydration increases with an increase in glyc- erol concentrations from 5 % to 10 %. Therefore, a good combination with regard to skin hydration is a cream of 5 % urea and 10 % glycerol [11].
Glycerol and urea in O/W emulsions not only improve hydration of the stratum corneum, but also protect the skin [14]. They can induce a skin protective barrier similar to a W/O emulsion [1]. Again, the com- bination of 5 % urea and 10 % glycerol seems beneficial [11]. Furthermore, glycerol in long-term experiments showed stabilization of the epidermal barrier function [12].
50.6
Vehicle Influence upon Biologic Effect of Topically Applied Drugs
The influence of the vehicle on the effect of topically applied drugs is manifold. The penetration rate of sali- cylic acid from a propylene glycol or oleic acid vehicle can be taken as 1. In a combined mixture of propylene glycol and oleic acid (equal parts), the penetration rate of salicylic acid is increased by a factor of 20 [2].
Urea can be detected in high concentrations after application of an O/W emulsion after a short time in the stratum corneum. However, even after longer application times, the concentration in deeper layers of the epidermis is low. This effect cannot be seen when W/O emulsions are used. However, after long-term application of a W/O emulsion, urea can be detected throughout the horny layer and the epidermal layers below [23]. When we use glycerin, the effect is differ- ent: glycerol in O/W emulsion leads to a more pro- nounced hydration of the stratum corneum [1].
In the topical treatment with glycocorticoids, the properties of the vehicle are crucial regarding the potency of the anti-inflammatory drug. In comparing betamethason valerate, triamcinolon acetonide, hydro- cortisone, and hydrocortisone acetate in unguentum leniens, basic cream DAC and Cold Cream Naturel (Roche Posay), all vehicles allowed a very good steroid effect. Triamcinolon acetonide was the most effective when applied in basic cream DAC; however, it could also be used in other vehicles. Hydrocortisone acetate in unguentum leniens or in Cold Cream Naturel did not show efficacy. This is different from hydrocortisone, which can be prescribed in basic cream DAC [7]. More pronounced differences can be found when using the nonsteroidal anti-inflammatory drug Fufexamac; here the spectrum ranges from absolutely no effect to accepted efficacy [7].
In general, lipophilic drugs penetrate more rapidly from lipophilic vehicles [19]. Therefore, evening prim- rose oil in hydrophilic or amphiphilic vehicles is not effective. In a lipophilic vehicle, it induces a stabiliza- tion of the epidermal barrier function in long-term application in atopic eczema [10].
466 50 Basic Topical Therapy with Emollients in Atopic Eczema
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