Drug administration The route of administration can be described as the path by which a substance is bought into contact with the body. There have been many advances in the formulations of drugs and the routes in which they are administered.

Drug administration

The route of administration can be described as the path by which a substance is bought into contact with the body. There have been many advances in the formulations of drugs and the routes in which they are administered.

Knowledge of the body’s transport mechanisms for this purpose and the way that drugs transport across tissues has also increased [1], Successful drug delivery systems are ones that increase safety and improve the overall performance of the drug, the pharmacokinetic properties of a drug critically influence the route of administration of drugs. New systems are constantly being researched and developed to help make simple the administration of the drug and therefore increasing patient compliance. Also the potential for greater flexibility in a variety of clinical situation exists which can be a benefit to certain patient groups such as children.

The development of different methods of drug administration has allowed physicians to deal with specific problems and to recognise the rapid onset, reliability and lack of patient discomfort when drugs are administered via routes such as transmucosally and transdermally [1].

When new methods or routes of drug administration are introduced, it is vital that the practitioner understand the pharmacologic actions of the administered drug and the pharmacokinetic and pharmacodynamic implications that may be unique for patients [1].

Transdermal administration

Transdermal drug administration is a method of delivery active drugs through the skin barrier [2]. It is therefore vital to understand the structure of the skin and the mechanisms by which drugs penetrate the skin and enter the blood stream [3]. A transdermal adhesive patch that can be placed on the skin and releases the drug through the skin into the bloodstream is the most common. An example of which is a nicotine patch, it contains nicotine and is used as an aid in quitting smoking. A wide range of pharmaceuticals can be delivered in this method, such as hormonal contraceptives and antidepressants.

Transdermal drug absorption can significantly alter drug kinetics and depends on a variety of factors including the following [1];

Site of application
Thickness and integrity of the stratum corneum epidermidis
Size of the molecule
Permeability of the membrane of the transdermal drug delivery system
State of skin hydration
pH of the drug
Drug metabolism by skin flora
Lipid solubility
Depot of drug in skin
Alteration of blood flow in the skin by additives and body temperature

There is a potential for toxicity when drugs are administered transdermally, as skin thickness and blood flow in the skin can vary with age. The relatively rich blood supply in the skin combined with thinner skin, have significant effects on the pharmacokinetics of transdermal delivery systems for children [1].

In some situations this may be an advantage, while in others systemic toxicity may result. Central nervous system toxicity occurred in neonates washed with hexachlorophene because their very thin skin and large body surface area allowed toxic levels to develop from systemic drug absorption. Physicians must consider such clinical implications of these factors when prescribing a drug to be ...

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When taken orally, many drugs are destroyed by the liver [3]. Hormones are also readily degraded and metabolised in the digestive tract and the liver. Hormones taken orally are often at a higher dose than those via transdermally administered and have their own limitations including hepatic first-pass metabolism [4]. Hence in this case a transdermal route has an advantage over other routes such as sublingual. Another advantage is that drug administration through the skin often provides a slower, more controlled alternative route for release into the blood stream [3].

Recent research shows attempts have been made to develop novel drug delivery systems for beta-blockers, including transdermal delivery systems, to circumvent the drawbacks of conventional drug delivery. Although no beta-blockers have been marketed in this form as of yet [4].

Transmucosal Routes

The respiratory tract, which includes the nasal mucosa, hypopharynx, and large and small airway structures, provides a large mucosal surface for drug absorption. Mucosal surfaces are the most common and convenient routes for delivering drugs to the body [5]. This route of administration is useful for treatment of pulmonary conditions and for delivery of drugs to distant target organs via the circulatory system [1]. The way in which drug absorption is improved via the mucosal surface is due to the absence of the stratum corneum ebidermis. The mucosal surfaces offer another advantage in the way that they provide a rich blood supply resulting in rapid drug transport to the systemic circulation, which allow an avoidance of first-pass hepatic metablism.

The amount of drug absorbed depends on the following factors [1]

Drug concentration
Vehicle of drug delivery
Mucosal contact time
Venous drainage of the mucosal tissues
Degree of the drug's ionization and the pH of the absorption site
Size of the drug molecule
Relative lipid solubility

Drugs that are delivered intranasally are used for a local effect and provide safety, efficacy and greater bioavailibility [9]. Vasopressin and corticosteroids were among the first drugs to be administered by this route [1]. Aerosol systems such as metered dose inhaler, dry powder inhalers and liquid jet or ultrasonic nebulizers are used for delivery of bronchodilators and corticosteroids for asthma or COPD (chronic obstructive pulmonary disease) [9]. The advantages of the nasal cavity is that provides a large surface area and easily accessible with highly permeable and vascularised tissue through which drugs can be absorbed rapidly and directly into the systemic circulation [6]. Nasal delivery also offers the advantage of avoidance of first-pass hepatic metabolism that consumes drug before it has chance to work [7] as well the opportunity to administer a smaller dose thus reducing the associated side effects [6]. Intranasal routes are non-invasive in comparison to injections and are patient friendly. This improves patient compliance and can allow the patient to self-medicate [7].

Due to the advantages that intranasal delivery offers there has been a substantial interest in using the alveolar surface as a portal to the systemic circulation for macromolecules such as proteins and peptides [9]. A number of small and macro-molecules administered systemically via the nasal cavity are now on the market [6]. However, some macromolecular drugs such as peptides and proteins are unable to overcome the mucosal barriers and/or are degraded before reaching the blood stream. Among the approaches explored so far in order to optimize the transport of these macromolecules across mucosal barriers, is the use of nanoparticulate carriers represents a challenging but promising strategy [5].

Drug developers and researchers are discovering that the accessibility and vascular structure of the nose make nasal drug delivery an attractive method for delivering both small molecule drugs and biologics, systemically as well as across the blood-brain barrier to the CNS [8]. Currently intranasal products are largely formulated as liquids and delivered via a metered pumped spray although this method is effective it can be limited by factors such as the solubility of the drug in the vehicle, the limited capacity of the nasal cavity to hold liquid without drainage to the throat or from its anterior portion, and the stability of the formulation [6].

Rectal Transmucosal Administration

Medications may be administered by the rectal mucosal route for systemic effects if other more preferable routes are not available for the treatment of nausea and vomiting, sedation, control of seizures, analgesia, or antipyresis [1]. The rectum offers a relatively constant environment for drug delivery provided the drug is presented in a well absorbable form [10] thus proving useful when infusion techniques are not available[12]. The rate and extent of rectal drug absorption are often lower than with oral absorption, possibly an inherent factor owing to the relatively small surface area available for drug uptake[11]. However, rectal administration of drugs should be avoided in immunosuppressed patients in whom even minimal trauma could lead to formation of an abscess [1] and cannot be used in patients with diarrhea, a colostomy, hemorrhoids, anal fissures or neutropenia.[12].

For a number of drugs the extent of rectal absorption has been reported to exceed oral values, which may reflect partial avoidance of hepatic first-pass metabolism after rectal delivery [11]. The most important concern for the practitioner is irregular uptake; clinically important patient-to-patient variability exist [12]. The absorption of the drug may be delayed or prolonged, or uptake may be almost as rapid as if an intravenous bolus were administered, which may cause adverse cardiovascular or central nervous system effects [1]. The rate of delivery may determine systemic drug action and side effects (nifedipine), and it may affect the local action of concurrently administered absorption promoters on drug uptake (cefoxitin) [11]. Prolonged use is not recommended because it is uncomfortable and the expulsion of the suppository by bowel movement will affect drug absorption [12].

Recent studies corroborate the clinical relevance of rectal drug therapy, and the value of the rectal route as an alternative to parenteral administration has been assessed for several drugs, e.g. diazepam, midazolam, morphine and diclofenac [11]. Current research has been conducted into the effects of rectal and vaginal administration of insulin gel formations on the blood glucose levels as alternative routes of administration[12].

References