Местные лекарственные средства: применение и особенности

Medication applied to body surfaces

A topical medication is a medication that is applied to a particular place on or in the body. Most often topical medication means application to body surfaces such as the skin or mucous membranes to treat ailments via a large range of classes including creams, foams, gels, lotions, and ointments. Many topical medications are epicutaneous, meaning that they are applied directly to the skin. Topical medications may also be inhalational, such as asthma medications, or applied to the surface of tissues other than the skin, such as eye drops applied to the conjunctiva, or ear drops placed in the ear, or medications applied to the surface of a tooth. The word topical derives from Greek τοπικός topikos, "of a place".

Topical drug delivery is a route of administering drugs via the skin to provide topical therapeutic effects. As skin is one of the largest and most superficial organs in the human body, pharmacists utilise it to deliver various drugs. This system usually provides a local effect on certain positions of the body. In ancient times, people used herbs to put on wounds for relieving the inflammatory effect or as pain relievers. The use of topical drug delivery system is much broader now, from smoking cessation to beauty purposes. Nowadays, there are numerous dosage forms that can be used topically, including cream, ointment, lotion, patches, dusting powder and much more. There are many advantages for this drug delivery system – avoiding first pass metabolism which can increase its bioavailability, being convenient and easy to apply to a large area, being easy to terminate the medication and avoiding gastro intestinal irritations. All these can increase the patient compliance. However, there are several disadvantages for this system – causing skin irritations and symptoms like rashes and itchiness may occur. Also, only small particles can pass through the skin, which limits the choice of drugs. Since skin is the main medium of topical drug delivery system, its conditions determine the rate of skin penetration leading to affecting the pharmacokinetics of the drug. The temperature, pH value and dryness of the skin need to be considered. There are some novel topical drugs in the market which can utilise the system as much as possible. This localized system provides topical therapeutic effects via skin, eyes, nose and vagina to treat diseases. The most common usage is for local skin infection problems. Dermatological products have various formulations and range in consistency though the most popular dermal products are semisolid dosage forms to provide topical treatment.

Topical drug absorption depends on two major factors – biological and physicochemical properties. The first factor concerns body structure effects on the drugs. The degradation of drugs can be affected by the site of applications. Some studies discovered different Percutaneous absorption patterns. Apart from the place, age also affects the absorption as the skin structure changes with age. The lowered collagen and broadened blood capillary networks happen with ageing. These features alter the effectiveness of absorption of both hydrophilic and lipophilic substances into stratum corneum underneath the surface of skin. The skin surface integrity can also affect the permeability of drugs such as the density of hair follicles, sweat glands or disintegrated by inflammation or dehydration. The other factor concerns metabolism of medications on skin. When the percutaneous drug is applied on skin, it will be gradually absorbed down the skin. Normally, when the drugs are absorbed, they will be metabolised by various enzymes in our body and the amount will be lower. The exact amount delivered to the target action site determines the potency and bioavailability of the drugs. If the concentration is too low, the therapeutic effect is impeded; if the concentration is too high, drug toxicity may happen to cause side effects or even do harm to our body. For the topical drug delivery way, degradation of drugs in skin is very low compared to liver. The metabolism of drugs is mainly by metabolic enzyme cytochrome P450, and this enzyme is not active in skin. The CYP450 actively metabolized drugs can then maintain high concentration when being applied on skin. Despite CYP450 enzyme action, the partition coefficient (K) determines the activity of topical drugs. The ability of drug particles to go through the skin layer also affects the absorption of drugs. For transdermal activity, medicines with higher K value are harder to get rid of the lipid layer of skin cells. The trapped molecules then cannot penetrate into the skin. This reduces the efficacy of the transdermal drugs. The drugs target cells underneath the skin or need to diffuse into blood capillary to exert their effect. Meanwhile, the size of particles affects this transdermal process. The smaller the drug molecules, the faster the rate of penetration. Polarity of the drugs can affect this diffusion rate too. If the drug shows lower degree of ionization, it is less polar. Therefore, it can have a faster absorption rate.

The definition of the topical route of administration sometimes states that both the application location and the pharmacodynamic effect thereof is local. In other cases, topical is defined as applied to a localized area of the body or to the surface of a body part regardless of the location of the effect. By this definition, topical administration also includes transdermal application, where the substance is administered onto the skin but is absorbed into the body to attain systemic distribution. Such medications are generally hydrophobic chemicals, such as steroid hormones. Specific types include transdermal patches which have become a popular means of administering some drugs for birth control, hormone replacement therapy, and prevention of motion sickness. One example of an antibiotic that may be applied topically is chloramphenicol. If defined strictly as having local effect, the topical route of administration can also include enteral administration of medications that are poorly absorbable by the gastrointestinal tract. One poorly absorbable antibiotic is vancomycin, which is recommended by mouth as a treatment for severe Clostridium difficile colitis.

A medication's potency often is changed with its base. For example, some topical steroids will be classified one or two strengths higher when moving from cream to ointment. As a rule of thumb, an ointment base is more occlusive and will drive the medication into the skin more rapidly than a solution or cream base. The manufacturer of each topical product has total control over the content of the base of a medication. Although containing the same active ingredients, one manufacturer's cream might be more acidic than the next, which could cause skin irritation or change its absorption rate. For example, a vaginal formulation of miconazole antifungal cream might irritate the skin less than an athlete foot formulation of miconazole cream. These variations can, on occasion, result in different clinical outcomes, even though the active ingredient is the same. No comparative potency labeling exists to ensure equal efficacy between brands of topical steroids (percentage of oil vs water dramatically affect the potency of topical steroid). Studies have confirmed that the potency of some topical steroid products may differ according to manufacturer or brand. An example of this is the case of brand name Valisone cream and Kenalog cream in clinical studies have demonstrated significantly better vasoconstrictions than some forms of this drug produced by generic drug manufacturers.

Foam can be seen with topical steroid marketed for the scalp.

Gels are thicker than liquids. Gels are often a semisolid emulsion and sometimes use alcohol as a solvent for the active ingredient; some gels liquefy at body temperature. Gel tends to be cellulose cut with alcohol or acetone. Gels tend to be self drying, tend to have greatly variable ingredients between brands, and carry a significant risk of inducing hypersensitivity due to fragrances and preservatives. Gel is useful for hairy areas and body folds. In applying gel one should avoid fissures in the skin, due to the stinging effect of the alcohol base. Gel enjoys a high rate of acceptance due to its cosmetic elegance. is either the pure drug by itself (talcum powder), or is made of the drug mixed in a carrier such as corn starch or corn cob powder (Zeosorb AF – miconazole powder). Can be used as an inhaled topical (cocaine powder used in nasal surgery).

A shake lotion is a mixture that separates into two or three parts over time. Frequently, an oil mixed with a water based solution needs to be shaken into suspension before use and includes the instructions: "Shake well before use".

Medication may be placed in a solid form. Examples are deodorant, antiperspirants, astringents, and hemostatic agents. Some solids melt when they reach body temperature (e. g. rectal suppositories).

Certain contraceptive methods rely on sponge as a carrier of a liquid medicine. Lemon juice embedded in a sponge has been used as a primitive contraception in some cultures.

Cordran tape is an example of a topical steroid applied under occlusion by tape. This greatly increases the potency and absorption of the topical steroid and is used to treat inflammatory skin diseases.

A tincture is a skin preparation that has a high percentage of alcohol. It would normally be used as a drug vehicle if drying of the area is desired.

Transdermal patches can be a very precise time released method of delivering a drug. Cutting a patch in half might affect the dose delivered. The release of the active component from a transdermal delivery system (patch) may be controlled by diffusion through the adhesive which covers the whole patch, by diffusion through a membrane which may only have adhesive on the patch rim or drug release may be controlled by release from a polymer matrix. Cutting a patch might cause rapid dehydration of the base of the medicine and affect the rate of diffusion.

Some medications are applied as an ointment or gel, and reach the mucous membrane via vaporization. Examples are nasal topical decongestants and smelling salt.

Topical drug classification system (TCS) is proposed by the FDA. It is designed from the Biopharmaceutics Classification System (BCS) for oral immediate release solid drug products which is very successful for decades. There are 3 aspects to assess and 4 classes in total. The 3 aspects include qualitative (Q1), quantitative (Q2) and similarity of in vitro release (IVR) rate (Q3). People found that applying medicines on the body surfaces is beneficial in many aspects. Skin medicines can give faster onset and local effect on our body as the surface cream can bypass first pass metabolism such as hepatic and intestinal metabolism. Apart from the absorption, dermal drugs effectively prevent oral delivery limitations such as nausea and vomiting and poor appliances due to unpalatable tastes of the drugs Topical application is an easy way for patients to tackle skin infections in a painless and non invasive way. From a patient perspective, applying drugs on skin also provides stable dosage in blood so as to give the optimal bioavailability and therapeutic effects. In case of overdose or unwanted side effects, patients can take off or wash out the medicines quickly to eliminate toxicity by simply removing the patch to stop the delivery of drugs.

The site of putting the patches for topical drugs may get irritated and have rashes and feel itchy. Hence, some topical drugs including nicotine patches for smoking cessation are advised to change places for each application to avoid continuous irritation of the skin. Also, since the drug needs to penetrate the skin, some drugs may not be able to pass through the skin. Some drugs are then “wasted” and the bioavailability of the drug will decrease.