A drug used on the skin must be dissolved or sus-pended in a vehicle (base). The choice of the drug and of the vehicle are both important and depend on the diagnosis and the state of the skin. For a drug to be effective topically, it must pass the barrier to diffusion presented by the horny layer . This requires the drug to be transferred from its vehicle to the horny layer, from which it will diffuse through the epidermis into the papillary dermis. Passage through the horny layer is the rate-limiting step.
The transfer of a drug from its vehicle to the horny layer depends on its relative solubility in each (measured as the ‘partition coefficient’). Movement across the horny layer depends both upon the concentration gradient and on restricting forces (its ‘diffusion constant’). In general, non-polar substances penetrate more rapidly than polar ones. A rise in skin temperature and in hydration, both achieved by covering a treated area with polyethylene occlusion, encourages penetration.
Some areas of skin present less of a barrier than do others. Two extreme examples are palmar skin, with its impermeable thick horny layer, and scrotal skin, which is thin and highly permeable. The skin of the face is more permeable than the skin of the body. Body fold skin is more permeable than nearby unoc-cluded skin. In humans, absorption through the hair follicles and sweat ducts is of little significance and the amount of hair on the treated site is no guide to its permeability.
In many skin diseases, the horny layer becomes abnormal and loses some of its barrier function. The abnormal nucleated (parakeratotic) horny layers of psoriasis and chronic eczema, although thicker than normal, have lost much of their protective qualities. Water loss is increased and therapeutic agents penet-rate more readily. Similarly, breakdown of the horny layer by chemicals (e.g. soaps and detergents) and by physical injury will allow drugs to penetrate more easily.
In summary, the penetration of a drug through the skin depends on the following factors:
• its concentration;
• the base;
• its partition coefficient;
• its diffusion constant;
• the thickness of the horny layer;
• the state, including hydration, of the horny layer; and
These include corticosteroids, tar, dithranol, anti-biotics, antifungal and antiviral agents, benzoyl per-oxide, retinoic acid and many others. The choice depends on the action required, and prescribers should know how each works. As topical steroids are the mainstay of much local derma-tological therapy, their pharmacology is summarized in Table 23.2.
Most vehicles are a mixture of powders, water and greases (usually obtained from petroleum). Figure 23.3 shows that blending these bases together produces preparations that retain the characteristics of each of their components.
vehicle should maximize the delivery of top-ical drugs but may also have useful
properties in its own right. Used carelessly, vehicles may even do harm.
Suggested indications are shown in Table 23.3. The choice of vehicle depends
upon the action desired, availability, messiness, ease of application and cost.
Dusting powders are used in the folds to lessen fric-tion between opposing surfaces. They may repel water (e.g. talc) or absorb it (e.g. starch); zinc oxide powder has an absorptive power midway between these extremes. Powders ought not be used in moist areas where they tend to cake and abrade.
Watery lotions evaporate and cool inflamed areas. This effect is hastened by adding an alcohol, but glyc-erol or arachis oil slow evaporation and retain skin moisture. Substances that precipitate protein (astrin-gents; e.g. silver nitrate) lessen exudation.
Shake lotions are watery lotions to which powder has been added so that the area for evaporation is increased. These lotions dry wet weeping skin. When water has evaporated from the skin, the powder particles clump together and may become abrasive. This is less likely if an oil such as glycerol has been added.
Creams are used for their cooling, moisturizing and emollient effects. They are either oil-in-water emulsions [e.g. aqueous cream (UK), acid mantle cream (USA)] or water-in-oil emulsions [e.g. oily cream (UK), cold cream (USA)]. Emulsifying agents are added to in-crease the surface area of the dispersed phase and that of any therapeutic agent in it.
Ointments are used for their occlusive and emol-lient properties. They allow the skin to remain supple by preventing the evaporation of water from the horny layer. There are three main types:
1 those that are water-soluble (macrogols, polyethy-lene glycols);
2 those that emulsify with water; and
3 those that repel water (mineral oils, and animal andvegetable fats).
Pastes are used for their protective and emollient properties and usually are made of powder added to a mineral oil or grease. The powder lessens the oil’s occlusive effect.
Variations on these themes have led to the numer-ous topical preparations available today. Rather thanuse them all, and risk confusion, doctors should limit their choice to one or two from each category. Table 23.3 summarizes the properties and uses of some common preparations.
Water-in-oil emulsions, such as ointments, require no preservatives. However, many creams are oil-in-water emulsions that permit contaminating organ-isms to spread in a continuous watery phase. These preparations therefore, as well as lotions and gels, require the incorporation of preservatives. Those in common use include the parahydroxybenzoic acid esters (parabens), chlorocresol, sorbic acid and propy-lene glycol. Some puzzling reactions to topical pre-parations are based on allergy to the preservatives they contain
Ointments and creams are usually applied sparingly twice daily, but the frequency of their application will depend on many factors including the nature, severity and duration of the rash, the sites involved, conveni-ence, the preparation (some new local steroids need only be applied once daily; Formulary 1) and, most important, on common sense. In extensive erup-tions, a tubular gauze cover keeps clothes clean and hampers scratching (see Fig. 7.19).
Three techniques of application are more special-ized: immersion therapy by bathing, wet dressings (compresses) and occlusive therapy.
Once-daily bathing helps to remove crusts, scales and medications. After soaking for about 10 min, the skin should be rubbed gently with a sponge, flannel or soft cloth; cleaning may be made easier by soaps, oils or colloidal oatmeal.
Medicated baths are occasionally helpful, the most common ingredients added to the bath water being bath oils, antiseptics and solutions of coal tar.
After cleaning, the most important function of a bath is hydration. The skin absorbs water and this can be held in the skin for some time if an occlusive oint-ment is applied after bathing.
Older patients may need help to get into a bath and should be warned about falling if the bath contains an oil or another slippery substance.
These are used to clean the skin or to deliver a topical medication. They are especially helpful for weeping, crusting and purulent conditions such as eczema,. Five or six layers of soft cloth (e.g. cotton gauze) are soaked in the solution to be used; this may be tap water, saline, an astringent or antiseptic solution, and the compress is then applied to the skin. Open dressings allow the water to evaporate and the skin to cool. They should be changed frequently, e.g. every 15 min for 1 h.
Closed dressings are covered with a plastic (usually polyethylene) sheet; they do not dry out so quickly and are usually changed twice daily. They are especially helpful for debriding adherent crusts and for draining exudative and purulent ulcers.
Sometimes steroid-sensitive dermatoses will respond to a steroid only when it is applied under a plastic sheet to encourage penetration. This technique is best reserved for the short-term treatment of stubborn localized rashes. The drawback of this treatment is that the side-effects of topical steroid treatment (Table 23.2) are highly likely to occur. The most important is systemic absorption if a large surface area of skin, relative to body weight, is treated (e.g. when steroids are applied under the polyethylene pants of infants).
One common fault is to underestimate the amount required. The guidelines given in Table 23.4 and Fig. 23.4 are based on twice daily applications. Lotions go further than creams, which go further than oint-ments and pastes.
Pump dispensers have recently become available for some topical steroids which allow measured amounts to be applied. Alternatively, ‘fingertip units’ (Fig. 23.5) can increase the accuracy of prescribing. As a guide, You know how much digoxin your patients are taking, but do you know how much of a topical corticosteroid they are applying? Keep a check on this.
one fingertip unit in an adult male from a standard nozzle provides 0.5 g ointment.