An Evaluation Of Dermal And Transdermal Drug Delivery Compared To Enteral Routes Of Administration

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An Evaluation Of Dermal And Transdermal Drug Delivery Compared To Enteral Routes Of Administration

Introduction

Over the last few years, there has been interest surrounding the development of conventional drug delivery systems with the aim of improving efficacy, safety and patient compliance of medications. In contrast to the typical enteral routes such as oral and sublingual administration, drug delivery through the skin is now being seen as an alternative and more convenient means of drug delivery via dermal and transdermal systems. These types of drug delivery embrace the means of delivering medications at a controlled rate across the skin for systemic distribution, and continue to accumulate vast amounts of innovation and investment with the continuous advancement of new approaches (1). Dermal, also known as topical administration, allows drug absorption at specific areas of the skin as a cream, ointment or lotion, thereby limiting systemic absorption. Transdermal administration delivers medication through the skin into the blood stream (10). Throughout this essay, I will be outlining the advantages and disadvantages of dermal and transdermal drug delivery and how they compared to oral and sublingual drug delivery respectively.

Transdermal vs Sublingual Delivery of Glyceryl Trinitrate

Glyceryl trinitrate (GTN) is commonly used to treat and also prevent angina. It works by causing vasodilation of the veins and arteries of the heart, making it easier to pump blood around the body (9). GTN is said to have a high hepatic first pass effect which means that if given orally, 96% the drug would be metabolised by the liver before reaching the rest of the body. Ultimately, this leads to low bioavailability of the drug as well as no therapeutic effect being produced. Therefore, glyceryl trinitrate is often administered either via a sublingual or transdermal route.

Transdermal patches contain a larger amount of the drug which is controlled to release the dose over either a day or several days. This method also ensures that the body has a consistent supply of the necessary medication (4). One of the advantages of transdermal drug delivery of GTN and the reason why this method of treatment has been gaining popularity over oral treatment is because when patients are expected to take pills multiple times every day, it increases the risk that they may miss doses, which can result in dangerous symptoms. In addition to this, the medication in the patches tends to last a long time before they need to be changed which can aid with compliance, especially with the elderly (4). Another advantage of transdermal administration is that it avoids the first-pass effect of metabolism associated with the oral route, which allows for improved bioavailability (10). In addition to this, a large surface area of skin and ease of access allows many placement options on the skin for transdermal absorption. It can improve patient compliance due to the reduction of dosing frequencies and is also suitable for patients who are unconscious or vomiting, or those who rely on self-administration (1). On the other hand, transdermal drug delivery can be unsuitable for some people because even when using them as prescribed and under physician supervision, skin irritation and sensitisation can occur. Under various environmental conditions, adhesions of the system to different skin types sometimes result in technical difficulties (3). Although transdermal administration appears promising it is not compatible with all medications (10) and the main disadvantage of them is that only drugs that are small enough to penetrate the skin can be delivered by this method (5).

Sublingual administration also has its advantages. GTN sublingual tablets are designed to dissolve quickly under the tongue. This area of the mouth has a large supply of blood vessels, and via this route, the drug is absorbed rapidly through the mucous membranes of the mouth and directly into the blood stream which provides effective relief from the pain of an angina attack (9). Conversely, the sublingual route also has some disadvantages. Eating, drinking, or smoking, can affect how the drug is absorbed and how well it works. Also, these forms dont work for drugs that need to be processed slowly by your system, such as extended-release formulations. Any open sores in your mouth can also become irritated by the medication (11).

Topical vs Oral Use of Diclofenac for Osteoarthritis

Osteoarthritis (OA) is a chronic condition, particularly in older people. Around 36% of those aged over 50 suffer from knee pain, half of whom have severe difficulty with physical function or severe pain. Analgesics and non-steroidal anti-inflammatory drugs (NSAIDs) are the most commonly prescribed drugs to relieve and control the painful flares experienced by sufferers of OA. Both topical and oral non-steroidal anti-inflammatory drugs (NSAIDs) are commonly used to treat this (7). A study was conducted to compare the effectiveness of topical vs oral use of Diclofenac to treat OA. Diclofenac was used in for this study because analysis suggests that it is the most potent COX-2 inhibitor compared with other commonly used NSAIDs. Topical drugs must be small enough to pass through the skin and Diclofenac is a small molecule (296 g/mol), allowing it to do so. Topical Diclofenac is proven to be effective in relieving the pain of OA, and there are various reasons to use a topical NSAID in preference to an oral NSAID. Gels, sprays and microemulsions may be absorbed through the skin more effectively than creams, and an in vitro study has suggested that Diclofenac gel has faster flux than a Diclofenac solution or patch (8).

An advantage of topical treatment is that the drug is delivered to the site of action, providing a more local effect and as a result may have fewer side effects due to lower serum concentrations (7). Dermal delivery of drugs often has similar efficacy and is potentially a more favourable tolerable. In addition to this, topical NSAIDs have been proven to be as effective as and better tolerated than oral NSAIDs in the treatment of OA, and are recommended in certain guidelines before the use of oral NSAIDs in OA of the knees or hands. In a preference study, almost three times as many OA patients chose to use a topical rather than oral NSAID, particularly those who were more concerned about toxicity such as the elderly (8). A meta-analysis of studies using topical NSAIDs concluded that they were more effective than placebo ointments for chronic musculoskeletal disorders at up to two weeks of use and that they were more preferable to oral ones as routine treatment for older patients with knee OA. Although a study showed that topical NSAIDs were proved to be effective up to two weeks of use, longer periods of use found that they were no more effective than placebo at three or four weeks of use (7). One other disadvantage is that in order to relieve pain effectively, topical NSAIDs need to work at the appropriate site of action. However, in OA there is still uncertainty regarding the target tissues and how OA-associated pain is generated (8).

On the other hand, the oral route has the advantage of pre-determined doses, portability and patient self-administration. For these reasons, the oral route remains the most convenient means of delivering medications (1). Oral administration remains the most commonly used route for medication. An oral medication generally becomes active when it passes from the gastrointestinal tract and the liver into the blood. Most newly approved medications are developed in oral forms to improve patient access and adherence (10). However, the risks of gastrointestinal effects, renal insufficiency and cardiovascular problems are higher with oral treatment of OA compared to dermal treatment (7). This can be an issue for older patients who form the OA population, who often have co-morbid conditions or an increased risk for gastrointestinal, cardiovascular or renal complications (8). Another disadvantage of the oral route is that it is unsuitable for patients who are uncooperative or who are vomiting profusely and the first-pass effect is involved which can reduce bioavailability of the drug. Furthermore, oral dosing can be inconvenient for elderly patients and they may have issues with co-operating or sticking to the dosing schedule.

Conclusion

To conclude, the main objective of transdermal drug delivery system is to deliver drugs into systemic circulation through skin at predetermined rate and is becoming a more promising delivery method for certain drugs. It eliminates the effect of drug degradation by the liver, has shown to enhance patient compliance and minimises harmful side effects (2). Looking at the second study and taking these factors into consideration, there is a sound rationale to use topical Diclofenac to relieve pain and inflammation in OA. The available evidence suggests that after topical application, the drug can penetrate the skin and permeate to deeper tissues, with generally higher levels in muscle than in plasma compared with oral administration. The concentrations achieved in the target tissues appear to be sufficient to exert a therapeutic effect. Thus, combined with its more favourable safety profile, there is a sound basis to use Diclofenac administered topically rather than orally (8).

Nevertheless, there is room for improvement with future formulations as the skin offers an accessible and convenient site for the administration of medications (1). Despite some studies claiming uncertainty, it is clear that dermal and transdermal drug delivery is pharmacologically effective, and patients report significant benefits comparable to oral administration (8).

References

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4695828/
https://ijpsr.com/bft-article/transdermal-drug-delivery-system-a-review/?view=fulltext
https://www.indiaparenting.com/womens-health/170_3256/benefits-and-drawbacks-of–transdermal-drug-delivery-systems.html
https://deserthopetreatment.com/addiction-guide/administration-methods/transdermal/
https://en.wikipedia.org/wiki/Transdermal_patch
https://en.wikipedia.org/wiki/Transdermal 10.1186/1471-2474-6-55
https://www.tandfonline.com/doi/full/10.1080/03007995.2017.1352497
https://www.netdoctor.co.uk/medicines/heart-blood/a6820/gtn-sublingual-tablets-glyceryl-trinitrate/
https://www.pharmacytimes.com/publications/issue/2016/August2016/Delivery-Methods-The-Patch-Versus-the-Oral-Route
https://www.healthline.com/health/sublingual-and-buccal-medication-administration#disadvantages

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