The Pharmaceutics and Compounding Laboratory
Ointments: Preparation and
Evaluation of Drug Release

Dermatological Formulations: Ointments and Pastes

Dermatological formulations are among the most frequently compounded products because of their wide range of potential uses. These include solutions (i.e., collodions, liniments, aqueous and oleaginous solutions), suspensions and gels, emulsions, lotions, and creams. Lotions can be either suspensions or emulsions but are fluid liquids that are typically used for their lubricating effect. Creams are emulsions and are typically opaque, thick liquids or soft solids used for their emollient properties. Creams also have the added feature that they tend to "vanish" or disappear with rubbing. Distinctions between lotions and creams are open to individual interpretation.

Other dermatological formulations that are not commonly compounded include aerosols, dusting powders, and devices such as transdermal patches, tapes, and gauzes. These formulations are typically manufactured.

This chapter will deal with two other dermatological formulations, ointments and pastes. Pastes have more solid material in them than ointments. These two formulations are also termed "semisolids" because they appear to be solid but still have fluid properties.

Local and Systemic Effects of Dermatological Formulations

Regardless of the formulation, all dermatological formulations are applied to the skin.

The skin is the largest and heaviest organ in the body and accounts for about 17% of a person's weight. Its major function is to protect the underlying organ systems from trauma, temperature, humidity, harmful penetrations, moisture, radiation, and microorganisms. It is composed of three layers of stratified tissue: epidermis, dermis, and subcutaneous tissue. The thickness of the skin is 3 - 5 millimeters. The thickness of the skin varies with the different parts of the body. The thickest parts of the skin are the palms and soles and the thinnest parts are the eyelids and genitals. Within the structure of the skin are several skin appendages: hair follicles, sebaceous glands, sweat glands, and nails.

In normal skin, the epidermal cells are continually replenished by the formation of initially viable cells from the basal germinative layer. As the new cells develop, they displace the outer epidermal cells. The outer layer is called the stratum corneum and these cells are sloughed off to the environment. As the cells migrate to become the stratum corneum, they become flattened, lose their nuclei, and the organized cell contents becomes replaced with keratin fibrils. The turnover time from germination to sloughing is about 21 days.

It is the stratum corneum that is the barrier to drug penetration through the skin. The stratum corneum is approximately 10 microns thick. It can swell to approximately three times its original thickness and absorb about five times its weight in water. When the stratum corneum hydrates, it becomes more permeable. Therefore, occlusive dressings are often used to hydrate the stratum corneum and increase the penetration of certain drugs. Dermatoses such as eczema and psoriasis can also hydrate the stratum corneum and increase the absorption of some drugs.

Dermatological formulations produce a local drug effect either on or in the skin. Besides the specific therapeutic action of incorporated active drugs, the formulations also as serve as protectants, lubricants, emollients, or drying agents. Examples of treatments using dermatological formulations include minor skin infections, itching, burns, diaper rash, insect stings and bites, athlete's foot, corns, calluses, warts, dandruff, acne, psoriasis, and eczema.

Some dermatological formulations are intended to systemically deliver a drug. Percutaneous (through the skin) absorption is the result of three competing processes:

  1. the potential of the drug to cross the stratum corneum
  2. the potential of the drug to leave the formulation
  3. the influence of the formulation on the stratum corneum.

Although the percutaneous absorption of drugs is a complex process, several generalizations are possible:

  1. More drug is absorbed when the formulation is applied to a larger surface area.
  2. Formulations or dressings that increase the hydration of the skin generally enhance percutaneous absorption.
  3. The greater the amount of rubbing in or inunction of the formulation, the greater the absorption.
  4. The longer the formulation remains in contract with the skin, the greater will be the absorption.

Percutaneous administration affords an ease of administration not found in other routes, and patient compliance is generally good with dermatological formulations. There is also the possibility of continuous drug administration exemplified by the transdermal patches. In addition, dermatological formulations can be easily removed if necessary.

The major disadvantage of this route of administration is that the amount of drug that can be absorbed will be limited to about 2 mg/day. This may become a significant limitation if the route is being considered for systemic therapy. However, several chemicals have been found that promote the percutaneous absorption of drugs. These "penetration enhancers" improve the solubility of the active drug in the stratum corneum and facilite the diffusion of the drug through this barrier into the systemic circulation. Below is a list of penetration enhancers used in dermatological formulations. (reference 1) Other commonly used enhancers include DMSO (dimethyl sulfoxide), urea, and triethanolamide.

Chemical Classification Examples
Alcohols methanol, ethanol, propanol, octanol
Fatty Alcohols myristyl alcohol, cetyl alcohol, stearyl alcohol
Fatty Acids myristic acid, stearic acid, oleic acid
Fatty Acid Ester isopropyl myristate, isopropyl palmitate
Polyols propylene glycol, polyethylene glycol, glycerol
Anionic surfactants sodium lauryl sulfate
Cationic surfactant benzalkonium chloride, cetylpyridinium chloride
Amphoteric surfactants lecithins
Nonionic surfactants Spans®, Tweens®, poloxamers, Miglyol®