Pediatric Annals

ISSUES IN TOPICAL THERAPY FOR CHILDREN 

The Importance of Vehicle in Pediatric Topical Therapy

David Orchard, MBBS; William L Weston, MD

Abstract

Topical medications are composed of two major components - the active ingrethent and the delivery system or vehicle. The correct prescription of both components is critical for successful topical therapy. This article aims to assist practitioners in prescribing topical preparations.

PERCUTANEOUS ADSORPTION

Absorption of topical medications through the epidermal barrier into the dermis is a complex process. In general, drugs that are water-soluble (because they are ions or polar molecules) penetrate an intact stratum corneum only minimally, whereas lipid-soluble compounds penetrate the stratum corneum more effectively. This is because molecules must travel between the tight intercellular spaces (of the stratum corneum cells) that contain almost entirely lipid-based substances.

Hydration of the skin allows water molecules to bind to hydrophobic intercellular lipids and therefore allows increased absorption of watersoluble medications. This can be achieved in several ways (eg, plastic wrap, another airtight occlusion, or including oils and ointments in the vehicle). Hydration can also be increased by adding particular chemicals such as urea and propylene glycol to topical medications because they interact with the intercellular lipids, enabling them to hold more water.

Other factors that can enhance percutaneous absorption include heat, inflammation, and dermatologic diseases that disrupt the stratum corneum.

THE COMPOSITION OF VEHICLES

The different types of powder, water, and ointment and their varying ratios give rise to a diverse number of vehicles. The most common preparations are mixtures of grease and water referred to as ointments, creams, lotions, or emulsions. Common grease ingrethents include petrolatum, mineral oil, lanolin, waxes, and polyethylene glycol. Liquid ingrethents include purified water, cetyl alcohol, propylene glycol, and glycerin. The grease component of these preparations protects the outer stratum corneum and allows it to retain water. This prevents scaling and increases percutaneous absorption. The liquid ingrethent is added to enable the grease to spread, making it more cosmetically pleasing and less occlusive. The more liquid that is added, the less viscous the preparation and the easier it will rub into the skin.

When a product is either mostly or totally grease, it is referred to as an ointment. When there is a high percentage of liquid, it is referred to as a cream or lotion. The ointments are better moisturizers and are the preferred vehicle for dry skin. However, they may contribute to heat retention, folliculitis, or acne, and are generally less cosmetically pleasing tor the patient. Any product that contains a liquid component requires a bacteriostatic ingrethent as a preservative and an emulsifier to enable the liquid and grease components to mix. These added ingrethents may sting, irritate, or cause an allergic contact dermatitis.

Gels are semisolid preparations with highmolecular-weight polymers and can be regarded as semiplastic aqueous lotions. They liquefy on contact with the skin and may burn and sting because of their alcoholic base. They permit good penetration of active ingrethents and are useful when skin is hairy or oily.

COMMON INGREDIENTS

Petrolatum, the base for most lubricants, is prepared from the residue remaining in the stills after the distillation of petroleum. It contains a mixture ot hydrocarbons, including triglycerides, and must be decolonized to make white petrolatum (petroleum jelly and white soft paraffin).

Liquid petrolatum (mineral oil and liquid paraffin) is a fluid phase of petrolatum obtained by distilling the residual petroleum liquid at 3300F and decolorizing it. It is the predominant ingrethent in baby oil and bath oil and, because it is in a fluid form at room temperature, is added to preparations in which easy spread on the skin is desirable.

Lanolin is a purified fat-like substance obtained from the wool of sheep. It contains up to 30% water…

Topical medications are composed of two major components - the active ingrethent and the delivery system or vehicle. The correct prescription of both components is critical for successful topical therapy. This article aims to assist practitioners in prescribing topical preparations.

PERCUTANEOUS ADSORPTION

Absorption of topical medications through the epidermal barrier into the dermis is a complex process. In general, drugs that are water-soluble (because they are ions or polar molecules) penetrate an intact stratum corneum only minimally, whereas lipid-soluble compounds penetrate the stratum corneum more effectively. This is because molecules must travel between the tight intercellular spaces (of the stratum corneum cells) that contain almost entirely lipid-based substances.

Hydration of the skin allows water molecules to bind to hydrophobic intercellular lipids and therefore allows increased absorption of watersoluble medications. This can be achieved in several ways (eg, plastic wrap, another airtight occlusion, or including oils and ointments in the vehicle). Hydration can also be increased by adding particular chemicals such as urea and propylene glycol to topical medications because they interact with the intercellular lipids, enabling them to hold more water.

Other factors that can enhance percutaneous absorption include heat, inflammation, and dermatologic diseases that disrupt the stratum corneum.

THE COMPOSITION OF VEHICLES

The different types of powder, water, and ointment and their varying ratios give rise to a diverse number of vehicles. The most common preparations are mixtures of grease and water referred to as ointments, creams, lotions, or emulsions. Common grease ingrethents include petrolatum, mineral oil, lanolin, waxes, and polyethylene glycol. Liquid ingrethents include purified water, cetyl alcohol, propylene glycol, and glycerin. The grease component of these preparations protects the outer stratum corneum and allows it to retain water. This prevents scaling and increases percutaneous absorption. The liquid ingrethent is added to enable the grease to spread, making it more cosmetically pleasing and less occlusive. The more liquid that is added, the less viscous the preparation and the easier it will rub into the skin.

When a product is either mostly or totally grease, it is referred to as an ointment. When there is a high percentage of liquid, it is referred to as a cream or lotion. The ointments are better moisturizers and are the preferred vehicle for dry skin. However, they may contribute to heat retention, folliculitis, or acne, and are generally less cosmetically pleasing tor the patient. Any product that contains a liquid component requires a bacteriostatic ingrethent as a preservative and an emulsifier to enable the liquid and grease components to mix. These added ingrethents may sting, irritate, or cause an allergic contact dermatitis.

Gels are semisolid preparations with highmolecular-weight polymers and can be regarded as semiplastic aqueous lotions. They liquefy on contact with the skin and may burn and sting because of their alcoholic base. They permit good penetration of active ingrethents and are useful when skin is hairy or oily.

COMMON INGREDIENTS

Petrolatum, the base for most lubricants, is prepared from the residue remaining in the stills after the distillation of petroleum. It contains a mixture ot hydrocarbons, including triglycerides, and must be decolonized to make white petrolatum (petroleum jelly and white soft paraffin).

Liquid petrolatum (mineral oil and liquid paraffin) is a fluid phase of petrolatum obtained by distilling the residual petroleum liquid at 3300F and decolorizing it. It is the predominant ingrethent in baby oil and bath oil and, because it is in a fluid form at room temperature, is added to preparations in which easy spread on the skin is desirable.

Lanolin is a purified fat-like substance obtained from the wool of sheep. It contains up to 30% water and is otherwise composed of alcohol and acid esters and free fatty alcohols and acids. Its composition varies with humidity, temperature, and method of collection. Occasionally, it causes an allergic contact dermatitis.1

Polyethylene glycol (macrogol ointment) is a water-soluble ointment that is less greasy than the petrolatum-based ointments. It is added to disperse the mixture uniformly or for its solvent properties.

Glycerin is a fatty alcohol derived from triglycerides as a by-product of the manufacture of soap. It is a clear, colorless, sticky liquid that absorbs water from within the skin surface.

Propylene glycol is a useful solvent and good penetrant, especially for corticosteroid creams.2 It may also act as a keratolytic and a preservative, but is irritating at high concentrations.

Urea hydrates skin by dissolving hydrogen bonds and adding water-binding sites. High concentrations (20% or more) or improper mixing may result in urea crystals, which cause severe irritation.

Preservatives are bacteriostatic agents, fungistatic agents, or both that are added to preparations containing water to prolong the life of the product. Water-containing products that are advertised as "preservative free" do in fact contain preservatives. However, they are classified as either fragrances or emulsifying agents by their manufacturer for marketing purposes. Popular preservatives include parabens, formaldehyde, formaldehyde-releasing agents (imidazole ureas), sorbic acid, quaternary ammonium compounds, chloroxylenol, chlorocresol, and hexachlorophene. Preservatives may cause irritation or allergic contact dermatitis. Therefore, pure ointments are the preferred vehicles for children with sensitive skin.

Fragrances are added to cover any unpleasant smell from the basic product, or are purely for marketing purposes. They are the most common cause of allergic contact dermatitis in cutaneous preparations, so fragrance-free products should be encouraged.

Emulsifying agents are added to water-oil preparations to prevent the oil from separating from the water. They are termed water-oil emulsions when the aqueous phase is dispersed within an oily phase and oil-water emulsions for the opposite. Emulsification greatly increases the surface area of application, aids the penetration of certain active agents, and generally increases cosmetic acceptability.3 However, emulsifying agents may also irritate or cause allergic contact dermatitis.

ADDITIONAL INGREDIENTS

Apart from the vehicle, many creams and ointments advertise that they have a variety of plant extracts, herbs, and vitamins as ingrethents. As a general rule, these products are added purely for marketing. There is no proof that they provide additional medical benefit and, on occasion, they may be detrimental. For example, aloe vera has been shown to impede the healing of burn wounds when applied topically4; tea tree oil occasionally causes an allergic contact dermatitis5; and 8 of 11 creams advertised as including "Chinese herbs" contained varying concentrations of dexamethasone.6 Although common, the addition of vitamins C and E to topical preparations has no substantiated medical benefit, with the possible exception of some mild ultraviolet protection immediately following application.7 Practitioners should try to recommend and prescribe formulations without unnecessary ingredients, to limit such adverse reactions.

AMOUNT TO DISPENSE

Therapy often fails due to dispensing incorrect quantities and instructions. Patients with widespread skin disease who are prescribed small quantities tend to underapply their medication to prolong its use. Overmedication is expensive for the patient and third-party payers. Although there is some variation related to the type of vehicle, approximately 2 g of topical preparation is used for a single application to the hands, face, head, or anogenital area. For an arm or anterior or posterior aspect of the trunk, approximately 3 g is used per application. A leg requires 4 g, and 30 to 60 g is needed per application to cover the entire body. Therefore, twice daily application to the entire body surface for 2 weeks will consume up to 1.5 kg of preparation.

PRESCRIBING TIPS FOR THE CHILD WITH ECZEMA

Eczema, the most common dermatologie condition in the pediatric setting, requires specific instructions due to the altered state of the skin. Although children with eczema can vary considerably in their clinical presentations, a predisposition to skin irritation is universal. Therefore, it is imperative that topical preparations be kept bland and simple, and that agents with the capacity to irritate the skin be rninimized. General prescribing rules for treating these children are as follows8:

1. Prescribe adequate amounts (as above).

2. Demonstrate how to apply the medication to the patient.

3. Apply lubricants, topical steroids, or both to wet skin when possible. This aids in trapping water within the skin and penetration of the steroid molecule.

4. Substitute lubricant therapy for topical steroids when the disease is inactive. In particular, discourage the use of topical steroids solely for their lubricant effect or for post-inflammatory hyperpigmentation.

5. Use ointments rather than creams as a general rule. Ointments are superior lubricants, enhance drug penetration, and are less likely to cause stinging, irritation, and allergy. Creams should be applied to naturally moist or macerated areas and may have to be prescribed for the adolescent who will not apply ointments because of the oily film left on the skin.

6. Avoid superpotent steroids in children and use only hydrocortisone in the diaper area.

7. Moderately potent (or weaker) topical steroids, even when used for protracted periods of time over large areas of the body, will not suppress the adrenal-pituitary axis.9 Therefore, steroid creams are preferable to pulses of oral prednisolone, even if large quantities must be prescribed.

CONCLUSION

Practitioners should understand the delivery systems of topical preparations to make the most informed decision for their patients. Avoiding potentially irritating or allergenic ingrethents is key. Simplification of topical therapy should always be the goal.

REFERENCES

1. Clarke EVV. The water absorption properties of lanolin. Journal of the Society of Cosmetic Chemists. 1971;22:421-437.

2. Ponec M. Penetration of corticosteroids through the skin in relation to the vehicle. Dermatologica. 1976;152(suppl l):37-46.

3. Polano MK. Topical Skin Theraputics. Edinburgh, Scotland: Churchill Livingstone; 1984.

4. Kaufman T, Kalderon N, Ullmann Y, Berger J. Aloe vera gel hindered wound healing of experimental second-degree burns: a quantitative controlled study. / Burn Care Rehabil. 1988;9:156-159.

5. Rubel DM, Freeman S, Southwell IA. Tea tree oil allergy: what is the offending agent? Report of three cases of tea tree oil allergy and review of the literature. Australas J Dermatol. 1998;39:244-247.

6. Keane FM Munn SE, du Vivier AW, Taylor NF, Higgins EM. Analysis of Chinese herbal creams prescribed for dermatological conditions. BMJ. 1999318:563-564.

7. Keller KL, Fenske NA. Uses of vitamins A C, and E and related compounds in dermatology: a review. J Am Acad Dermatol. 199839:611-625.

8. Weston WL, Lane A. Practical Pediatric Dermatology, 2nd ed. Boston: Little Brown; 1979:365-387.

9. Ellison JA, Patel L, Ray DW, David TJ, Clayton PE. Hyporhalarnic-pituitary-adrenal function and glucocorticoid sensitivity in atopic dermatitis. Pediatrics. 2000;105:794-799.

10.3928/0090-4481-20010401-09

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