Topical Preparations and Vehicles

As a general consideration, the chemical agents that may be applied to the skin for their local effects belong to two categories: drugs and non-drugs

The agents of the first category have a selective action in terms of chemical and pharmacological activity on the skin. Antibiotics, antimycotics, corticosteroids and antineoplastics are some examples.

The second category is composed of a heterogeneous group of agents showing mostly a non-selective action, with limited chemical and pharmacological activity and, sometimes having just a functional action.

Therefore, excluding drugs, topical treatment may be subdivided into non-specific treatment with vehicles and specific treatment with active agents.

Dermatological bases or vehicles serve not only as vectors for incorporating active ingredients but also possess some para-therapeutic effects because of their own physicochemical properties.

Specific topical treatments are prescribed by dermatologists in so-called magistral formulations. In this case, the topical treatment consists of the local use of some active substances in a suitable vehicle. These locally acting agents include absorbents, astringents, demulcents, rubefacients, keratolytics, emollients and miscellaneous other ingredients.

General Principles and Classification

Dermatological therapy can be a combination of systemic and topical treatments although topical treatment is often the only therapy prescribed. Therefore, dermatologists must be familiar with the use of topical preparations, whether a drug or an active agent needs to be added or not. Tailor-made preparations have undoubtedly a great positive impact on patients, but their use is limited by two main factors: the poor confidence of practicing dermatologists to prescribe magistral preparations and the difficulty in finding pharmacists able and willing to provide them. In a recent analysis of compound prescriptions, some mixtures prescribed by dermatologists were questionable either because of the number of active ingredients or the selected concentrations. As a general consideration, the chemical agents that may be applied to the skin for their local effects belong to two categories:

• Drugs
• Non-drugs

The agents of the first category have a selective action in terms of chemical and pharmacological activity on the skin. Antibiotics, antimycotics, corticosteroids and antineoplastics are some examples. They are prepared by pharmaceutical companies according to strict international rules on suitable vehicles and are ready to use.

Their use in combination with other ingredients is neither recommendable nor economically worthwhile.

The second category is composed of a heterogeneous group of agents which, by exclusion, do not belong to the first. They have mostly a non-selective action, have limited chemical and pharmacological activity and, sometimes, have just a cosmetic action. These locally acting agents include absorbents, astringents, demulcents, rubefacients, keratolytics, emollients and miscellaneous other ingredients used in dermatology. The local treatment of skin disorders also includes the exclusive use of vehicles. Therefore, excluding drugs, topical treatment may be subdivided into:

• Non-specific treatment with bases (Vehicles only)
• Specific treatment with active agents into vehicles

Non-specific Treatment with Bases

Dermatological bases or vehicles serve not only as vectors for incorporating active ingredients but also possess some para-therapeutic effects because of their own physicochemical properties. In this case, the bases themselves are to be considered the active ingredients. The ideal base should have the following properties:

• Easy to apply and remove
• Non-toxic, irritant, or allergenic
• Chemically stable
• Pharmacologically inert
• Sensory acceptable

The bases can be liquid, semi-solid or solid. Some bases are utilized in non-specific dermatological treatment, while others are used as vehicles for active ingredients

Table 152.1 List of topical preparations, used as Bases or Vehicles for active ingredients

• Fatty Ointments
• Fatty pastes
• Powders
• Hydroalcoholic Lotions and Gels
• W/O (water in oil) Emulsions
• O/W (oil in water) Emulsions
• Oils

Another classification of vehicles can be based on their dispersed phase distribution: Monophasic, Biphasic, Polyphasic.

The main effects, clinical indications and contraindications of bases are discussed according to the categories listed in Table 152.1.

Fatty Ointments

Fatty ointments are anhydrous, lipophilic, and hydrophobic bases consisting of mineral, synthetic or natural origin fats. Paraffin, petrolatum, lanolin, castor oil, palm and olive oil are examples of fats used in ointments. The ointments cover the stratum corneum softening the skin and inhibiting to some extent drug penetration. They are useful for the treatment of dry skin, hyperkeratotic and scaling dermatoses.

The obstruction of the release of heat and water may produce maceration, increase inflammation, or produce dyshidrotic eruptions.

Fatty Pastes

Pastes are mixtures of powder and ointment or cream; depending on the powder concentration, they may be subdivided into Soft, Medium, and Hard pastes.

Zinc oxide, talc and wheat starch are the most utilized powders. The pastes have a cooling, anti-inflammatory and skin-protective action.

They are useful for the treatment of chronic dermatoses, especially when lichenification is present. Some of them have secretion absorbing or drying effects. The hard pastes have the same contraindications as ointments.

Powders

Powders are composed of micronized and dispersed granular particles. They can be homogeneously distributed on large body areas directly from a dusting can. Talc, zinc oxide, starch and magnesium carbonate are examples of the most used powders. They have protective antifriction activity together with cooling and drying effects. They are used in erythematous exanthems and in some pruritic conditions. They dry the skin absorbing water and lipids from the surface, and they crust the skin in oozing and erosive dermatoses.

Hydroalcoholic Lotions and Gels

Hydroalcoholic lotions are a mixture of ethanol or isopropanol and water. They are mostly used as vehicles for active substances but may be used alone for their defatting and drying effects. They are indicated in seborrheic conditions and contraindicated in xerotic and scaling dermatitis.

Hydroalcoholic gels are composed of cellulose compounds and derivatives, alginic acid and other gelling agents that swell with water or water/alcohol to produce a gelatinous base.

Hydroalcoholic gels have cooling and slight anti-inflammatory action so they are used in erythematous and pruritic exanthems as well as for the treatment of acute exogenous dermatitis. They may be applied to hairy parts but have a drying effect on prolonged application.

W/O Emulsions

Creams (W/O type) are a two-phase system of fatty substances, water and emulsifying agents. Usually, the fatty phase is higher than the water phase and have a consistent texture.

They are mainly used as vehicles for active substances, and due to the high concentration of fats, they have a smoothing and softening effect, together with slight cooling and anti-inflammatory action. For these properties, they are employed to  counteract xerotic, dry skin and to soften scales and crusts in chronic dermatoses.

They are less tolerated than O/W creams on seborrheic types of skin.

O/W Emulsions

O/W Emulsions usually have a lower fatty phase. They appear milky in colour and consistency and usually are used in cosmetics  for  cleansing  and  body/face  lotions. O/W Emulsions possess a slight anti-inflammatory, antipruritic effect and may be used even in exudative and vesicular dermatoses. However, they tend to dry the skin due to rapid evaporation of water. They are not suitable for chronic scaly dermatosis treatment.

Oils

Oils, as medical preparations, are used for dissolving fat-soluble active ingredients but may be used alone or for suspending powders. Oils have lubricating action and may be used to soften crusts and scales and to remove ointments and pastes. They are indicated in acute superficial dermatoses especially in children and are less indicated in adults especially with seborrhoea or seborrheic dermatoses.

In Table 152.2, the bases for dermatological non-specific treatment are listed. Some of these vehicles are rarely used mainly because of their poor cosmetic acceptability; only emulsions are largely used as vehicles for non-specific topical treatment. The most widely used cream in European countries is a base cream called cetomacrogol cream present in many pharmacopoeias.

Cetomacrogol cream consists of 30 % soft greases including soft white paraffin and petrolatum, the emulsifying agent, that is a condensation of cetostearyl alcohol with ethylene oxide.

Cetomacrogol cream is non-allergenic, non-greasy, washable, low cost and easy to prepare. Usually, it is prescribed as a vehicle for active ingredients, but it is useful in many non-specific treatments and even as a placebo.

Specific Treatment with Active Agents

Specific topical treatments are prescribed by dermatologists in so-called magistral formulations. In this case, the topical treatment consists of the local use of some active substances in a suitable vehicle. The vehicles are the same as proposed in the previous section, and the local acting agents may be differentiated by their specific activity on the skin. There is no international agreement about the terminology for describing activity of these compounds on the skin. Moreover, there is no clear distinction between drug and nondrug, so that the limit of a magistral prescription is not well defined.

Theoretically, all topical dermatological treatments can be carried out with extemporaneous preparations. However, some of them are technically difficult to prepare and economically not worthwhile.  Others are purchased from pharmaceutical companies and have a high safety profile. The main actions of topical active ingredients are listed in Table 152.3. The actions of active ingredients and the ingredients themselves are discussed in the following sections.

Protectives and Absorbents

Protectives and absorbents are intended to absorb moisture, decrease friction, discourage bacterial growth, and absorb fats, contributing to a decrease in body  odours.  These actions are achieved using powders and some protective agents. Powders considered for this activity are bentonite, calcium carbonate, talc, titanium dioxide, zinc oxide and zinc and magnesium stearate.  Other substances such as propylene glycol and glycerol may be added to increase the protective action.

Vaseline and silicones are examples of other chemical protectives.

Hydrophilic and lipophilic emulsions containing a variety of constituents, such as allantoin, linoleic acid, pantothenol, omega-3 oils, urea, and vitamins, have been considered by other authors to be protective. However, their activity has not been demonstrated yet.

Lenitives

Lenitives are employed to alleviate skin irritation in many superficial skin dermatoses. They also prevent drying of affected areas.

Lenitives are mainly in the form of lotions, wet dressings or simply powders. Alginates, mucilages, gums, dextrins, starches, certain sugars, glycerol and many oils are commonly considered as lenitives. Zinc oxide, talc and starch are sometimes added  for  their  astringent  anti-inflammatory effect.

Emollients

Emollients are used to render the skin softer and more pliable and also possess some anti-irritative properties. Oils of mineral, vegetable, and animal origin as well as waxes are considered emollients. Some vegetable fats, such as karite butter or jojoba liquid wax, possess both a good emollient and cosmetic acceptance. Both creams and ointments are suitable for this purpose. All ointments are considered emollients, and virtually all emulsions, due to the presence of fat components that penetrate easily into stratum corneum layers, are also emollients. For this reason, emulsions instead of ointments are now prescribed as emollients because of their better sensory properties.

Astringents and Antiperspirants

Astringents are active substances. When applied locally, they are protein precipitants, having low cell penetrability so that their action is limited to the surface. Astringents in dermatology are used to reduce erythema and pruritus; they also have an antiperspirant effect by causing protein precipitation in the sweat ducts. Astringents/antiperspirants also have deodorant properties due to an interaction with odorous fatty acids liberated by bacteria and by suppressing bacterial growth by virtue of low pH. The main astringents are:

• Salt of the cation’s aluminium, bismuth, iron, manganese, and zinc
• Other salts containing these metals such as permanganates
• Tannins or related polyphenolic compounds

Powders, lotions and gels are used for this purpose.

Aluminium chloride hexahydrate aqueous or hydroalcoholic solution 5-10 % may be used as an astringent in many chronic oozing dermatitis cases as well as an antiperspirant at concentrations of 10-20 %.

Antipruritics

Pruritus is a common symptom of different dermatoses of eczema, atopia, urticaria, exanthema type and neurodermitis type, etc. It can also be linked to internal diseases or skin senescence. Most astringents, keratoplastics or rubefacients possess antipruritic activity. Menthol, phenol, salicylic acid, and coal tar are used as topical antipruritic in different dermatoses.

Coal tar is an effective antipruritic agent and can be used in emulsion, like in cetomacrogol cream, at 2 %.

Rubefacients

Rubefacients are able to induce hyperaemia and slight inflammation that produces a feeling of  comfort,  warmth,  sometimes  itching and hyperaesthesia. Most rubefacients in high concentrations are vesicants. Rubefacients are sometimes used for treating the sensory and visible effect of irritation, giving the patient the impression of receiving an effective medication. They are also used to treat pernioses and to promote hair growth especially in alopecia areata. Examples are:

• Alcohol camphor
• Anthralin
• Capsicum
• Benzoin menthol
• Resorcinol
• Methyl salicylate
• Nicotine acid and its esters

Caustics

Caustics are agents that cause the destruction of tissue; therefore, they are used in hyperkeratosis or hyperplastic tissues, but they can be used also for the destruction of tumours such as basal cell carcinoma and xanthelasmas. These agents usually precipitate proteins so that they may be considered as astringents at low concentration. Caustics are also bactericidal. Examples are:

• Trichloroacetic acid
• Glacial acetic acid
• Phenol
• Silver nitrate
• Nitric acid
• Potassium hydroxide

Caustics are usually applied to the skin with a stick swab. Examples are:

• Trichloroacetic acid 50 % aqueous solution is used to remove xanthelasmas.
• Liquefied phenol 20 % in water to bleach hand freckles.

Keratolytics

Keratolytics loosen the keratins or intercellular cement facilitating desquamation of scales and softening horny material or crusts so they may be used in hyperkeratotic conditions. They also eliminate parasites or fungi. However, the real action of some keratolytics is not completely elucidated. Examples are:

• Salicylic acid
• Sulphur
• Urea
• Resorcinol
• Calcium chloride
• Some alkali-containing compounds such as sodium and potassium hydroxide.

Among these, salicylic acid is the most used in a variety of formulations. Around 6-10 % of salicylic acid is needed for a keratolytic effect even if the possibility of toxicity due to absorption has to be considered. Therefore, high concentrations are employed in very small areas incorporated in collodion.

Keratoplastics

Keratolytic agents at low concentrations stimulate the renewal of the horny layer through a slight reducing action and favouring desquamation.

Salicylic acid, Lactic, Glycolic And other alpha-hydroxy acids, sulphur, urea and ichthyols are considered keratoplastics.

Other ingredients are able, via a toxic event, to reduce DNA synthesis and mitosis, especially in hyperproliferative disorders. Some of these substances, namely, tars, also possess antipruritic-anti-inflammatory action so that they may be used in a variety of skin disorders ranging from psoriasis to atopic dermatitis.  This activity should be defined as a reducing activity, but many authors regard it as a keratoplastic activity. Examples of these compounds are coal tar, resorcinol, anthralin, ichthyol and phenols.

Coal tar can easily be incorporated into cetomacrogol cream up to 4 %. The result is a cosmetically acceptable and washable preparation, useful for outpatient treatment.

Cleansing

Cleansing may be carried out with detergents, solvents, abrasive substances singly or in combination. Soaps and shampoos are often used as vehicles for active agents such as antibacterial, antifungal, salicylic acid or tars. Cationic or amphoteric detergents, like benzalkonium chloride are also antibacterial.

Substances in this group include:

• sodium laurylether sulphate
• benzalkonium chloride
• alkyl amido betaine

Fluid O/W emulsions on cotton swabs are also suitable for cleansing affected skin or for removing topical medicaments or makeup.

Opacifying and Sebum Absorbing

Opacifying and sebum absorbing agents are used to diminish the brightness of oily or seborrheic skin. Some micronized powders by virtue of their absorbent properties have the action of physically absorbing secretion of both sweat and sebaceous glands. Examples are:

• Bentonite
• Zinc oxide
• Kaolin
• Titanium dioxide
• Magnesium Carbonate

Each of these compounds may be incorporated in lotions or O/W creams. The amount depends on the degree of micronization of the powder employed. Iron oxides may be added in small quantities to match the skin colour.

Exudate absorbing and bacterial growth controlling

A frequently used vehicle that is not classifiable as a base with non-specific activity is polyethylene glycol ointment. This ointment is classified as a hydro soluble ointment and is also called a greaseless ointment base.

This is composed of water-soluble constituents, namely, polyethylene glycols (PEG). PEG ointment is particularly useful because it is an inert, anhydrous, viscous compound that is completely washable. It is possible to incorporate into a PEG ointment almost all active ingredients and distribute them to all body areas, hairy parts included.

Wash ability of this ointment makes it very acceptable to patients. PEGs are hydrophilic compounds and, when applied to eroded or ulcerated skin, exert an absorbing action on exudates and are usually well tolerated. PEGs do not have cellular toxicity and do not interfere with cell growth and migration during the tissue repair process. Moreover, the use of PEG dressing enables anti adherence and water vapour permeability properties. For these reasons, PEG ointment must be considered the ideal dressing for dermatological surgery.

To reach the desired consistency, the ratio of the high and low Molecular Weight polymers can be variable. In the treatment of ulcers, allantoin, which induces healing by stimulating healthy granulations and removing necrotic material, is usually added to PEG ointments up to 5 %. New medication based on PEG-allantoin-soaked gauze will be useful and practical in the dressing of surgical wounds as well as of ulcers. Allantoin-PEG ointment is stable and nontoxic, and the treatment of ulcers is painless, simple, and inexpensive.