INTRODUCTION:

Often named "patches" transdermal technology for drug delivery systems are pharmacological formulations that have been specifically developed to deliver a therapeutically useful amount of medication through a patient's skin. It is a method for delivering medicine into the circulatory system through the skin. The scopolamine patch, which was sold under the Transdermal Scop brand, was the first transdermal patch product ever approved by the FDA in 1981.

Many drugs, including as fentanyl for chronic pain, clonidine and nitroglycerine for cardiovascular conditions, scopolamine for motion sickness, and nicotine for quitting smoking, can already be delivered using commercial transdermal systems. Because they provide continuous distribution and reduce pulsatile systemic exposure, these patches are especially beneficial for medications with short biological half-lives, allowing for controlled and prolonged pharmacological effect¹. Many conditions, including hypertension, rheumatoid arthritis, diabetes mellitus, psychiatric disorders, motion sickness, migraines, neurological disorders, and smoking cessation, can be controlled and treated with transdermal medications².

Two common extended-release dose forms are medicated plasters and transdermal patches. Notwithstanding their importance, reports of inadequate in vivo adhesion are regularly sent to regulatory bodies, which has a direct bearing on the safety and effectiveness of treatments. Tack, shear adhesion, and peel adhesion are three crucial factors to take into account when describing the adhesive qualities of patches. Peel adhesion quantifies the effort needed to remove the patch, shear adhesion evaluates resistance to flow, and tack indicates the capacity to make an instantaneous bond under minimal pressure. These elements are essential for assessing the efficacy and dependability of medicated plasters and transdermal patches in clinical settings.³

Advantages:

1. Increases bioavailability by avoiding hepatic and pre systemic metabolism.

2. You won't have to deal with the hassles and hassles of IV therapy.

3. Less frequent administration of the dose.

4. Simple cessation of pharmacotherapy occurs upon the removal of the patch.

5. Improve patient compliances.

6. Enhanced treatment efficacy by circumventing the fluctuations in systemic medication concentrations linked to traditional drug administration methods.

7. Self-administration is feasible.

8. Minimization of side effects.⁴

Disadvantages:

1. Only powerful compounds are appropriate options for transdermal administration.

2. Certain individuals may develop irritation at the application site.

3. It is inappropriate for medications necessitating elevated blood concentrations.⁵

1. Transdermal Patch Design:

Multiple variables, including skin permeation, site and duration of application, and skin cellular activity (i.e., first-pass metabolism), affect medication transdermal transport. Actually, each medication has distinct qualities that may influence transdermal administration. The medication must be non-ionic and somewhat lipophilic to penetrate the skin barrier and achieve sufficient skin absorption and penetration. Because it is difficult for molecules that are larger than 500 Daltons to get through the stratum corneum, the medicinal dosage of the medicine should preferably be less than 10mg per day.

1.1 Basic Component of Transdermal Patch:

In most cases, transdermal patches are made up of multiple layers, each of which is intended to carry the medication via the skin to the circulatory system.

Fig 1: Elements of Transdermal Patches

Liner:

It protects the patch while it is being stored. Before using, the liner should be taken out. It is a component of initial packing that prevents the medicine from escaping the polymer matrix.

Adhesive:

This part is used to secure the patch to the skin and tie its components together. Examples of adhesives include Polyacrylate, Polyisobutadiene, and Silicon-based adhesive polymers.

Membrane:

The membrane regulates medication release from reservoirs and multi-layer patches. Usually, chitosan and poly-2-hydroxyethylmethacrylate are used to make it. Examples include silicones, polyester polyacrylonitrile, ethylene vinyl acetate copolymer, and high-density polyethylene.

Drug:

The active substance is in close proximity with the release membrane.

Polymer:

The polymer itself has to demonstrate chemical and biological tolerance with pharmaceuticals and other ingredients such as adhesives, plasticisers, and enhancers of permeation. For example:

1. Natural polymers: Shellac, gelatin, chitosan, waxes, cellulose derivatives, natural rubber.

2. Synthetic polymer: PVA, polyurea, polyamide, polyethylene, polyvinyl pyrrolidone, polypropylene.

3. Synthetic elastomer: Polyurethane, polyisobutylene, polybutadiene, nitril, hydrin rubber, silicon rubber, butylrubber.

Backing:

It shields the patch from the elements, supports the patches, and gives them flexibility and a nice look.⁶

Permeation Enhancers:

The chemical components that enhance the ability to penetrate of the stratum corneum to attain medicinal drug concentrations. Penetration enhancers augment penetration by interacting with the stratum corneum.

Optimal Characteristics:

· Environmentally friendly, gentle on the skin, and non-allergenic.

· It ought not to bind to the receptor location.

Pressure Sensitive Adhesive (PSA):

Adherence of transdermal patch to the skin surface is increase by glue that responds to pressure. The major criteria for pressure sensitive adhesive is it ought to be readily removable from its smooth surface and leave no residue on it. E.g. Silicon based adhesives and polyacrylates.

Plasticizers:

They are used to reduce brittleness of polymer film. E.g. Glycerol, polyethylene glycol, propylene glycol.

1.2. Types of Transdermal Patch:

The four basic varieties of transdermal medical patches are known as drug-in adhesive, reservoir, matrix, and micro-reservoir systems each having their own unique characteristics. The most popular types of patches that are offered for sale commercially are reservoir or matrix systems.

1. Adhesive Drug System: This is the most fundamental kind of membrane permeability control mechanism. Drugs are included in the adhesive layer of this system, which keeps the various layers together. The drug mixture is put on top of the backing and liner.⁷

2. Reservoirs System: Within this structure, the drug reservoir is held in place between the membrane and the backing layer, and the drug is released through the microporous membrane that regulates the pace at which it is released. The medication may be dispersed in a solid polymer matrix, or it may be present in the reservoir chamber as a gel, suspension, or solution. Alternatively, it may be delivered in any solid form.

3. Matrix system: Drugs are uniformly dispersed across hydrophilic or lipophilic polymer matrices. The resulting drug-containing polymer is adhered to drug-containing discs with controlled thickness and surface area.

4. Micro-Reservoir System (Multilaminate):

This system combines a reservoir with a matrix dispersion system. Here, drug solids are suspended in an aqueous solution of a water-soluble liquid polymer, and the solution is then evenly dispersed in a lipophilic polymer to create millions of non-leaching small drug reservoirs.

5. Vapour Patch: This patch's sticky layer serves two functions: In addition to releasing vapors, it holds the various layers together. These vapor patches are primarily and frequently used for decongestion. These vapor patches emit essential oils for a maximum of six hours. Certain vape patches are made to help people sleep better.3quality and assist individuals in quitting smoking.⁸

6. Microneedle-Based Patches: Table 1 lists the various kinds of microneedles, each having special traits and attributes. Solid, hollow, dissolving, and coated microneedles are the four main varieties of microneedle-based patches that have been created thus far (Figure 3). The particular application and the user's needs determine the type of microneedle to utilize.

Fig 2: Microneedle type with their Unique Features

Coated Microneedles:

The coating on these microneedles breaks when the skin is penetrated, releasing medications or other materials. Transdermal medication administration frequently uses coated microneedles.

Hollow Microneedles:

The hollow core of these microneedles makes it possible to inject medications or fluids into the skin. Hollow microneedles are frequently employed for interstitial fluid collection and transdermal medication administration.

Solid Microneedles:

The most basic kind of microneedles are made of solid needles that pierce the skin to form microscopic channels. Drug administration and cosmetic procedures are two common uses for solid microneedles.

Dissolving Microneedles:

The materials used to make these microneedles dissolve in the skin, enabling the controlled delivery of medications or other substances. Applications for dissolving microneedles in medication administration, including vaccinations, are common.

Fig 3: Different types of patches

Recent Advancement of Transdermal Patch:

Smart Patches:

Sensors and other technology included into smart patches allow them to track patient status and modify medication distribution as necessary. A smart insulin-releasing patch made of 121 microneedles with nanoparticles was the product of research and development. The patch enters the interstitial fluid between subcutaneous skin cells without causing any discomfort. Insulin and the glucose-sensing enzyme glucose oxidase, which changes glucose into gluconate, are found in the nanoparticles in each needle. Hypoxia-responsive polymers envelop these molecules. Figure 4 illustrates this. Medicina 2023, 59, x for peer reviews the hypoxia-responsive polymer detects the oxygen 7 of 22 deprived environment created by increased glucose oxidase activity in response to elevated glucose, which causes the nanoparticles to degrade and release insulin.^22,23

Dissolving/Degradable Patches:

These patches don't need to be taken off and thrown away because they are made to disintegrate on the skin. These patches are often composed of biodegradable substances that the body absorbs after usage. In a 2019 proof-of-concept study, scientists used a dissolving patch to successfully give the antibiotic gentamicin to a mouse model of bacterial illness.²⁴

Three-Dimensional (3D)-Printed Patches:

Transdermal patches that are personalized to each patient's needs can be made using 3D printing technology.²⁵ The use of a 3D-printed patch for wound healing is a nice example. Gelatin methacrylate (GelMA) was examined as a potential solution with adjustable physical characteristics in a research by Jang. Because hydrogel inks shear thin, GelMAhydrogel, which contains a peptide that mimics vascular endothelial growth factor (VEGF), was effectively printed using a 3D bio-printer. The hydrogel patch's three-dimensional structure exhibited significant porosity and water-absorption capabilities. The 3D Gel-MA-VEGF hydrogel patch may be utilized as a wound dressing because the VEGF peptide, which is gradually released from hydrogel patches, can encourage cell survival, proliferation, and tubular structure creation.²⁶

High Loading/Release Patches:

A new pressure-sensitive adhesive (PSA) modified with hydroxyphenyl (HP) was created to enhance drug-polymer miscibility and regulate drug release in transdermal patches. Because of the reversible and somewhat strong dual-ionic H-bonds that exist between HP-PSA and pharmaceuticals of the R (3)N and R (2) NH types, patches can greatly enhance drug loading and regulate drug release rates without altering the overall release profile. The HP-PSA-based high-load patch enhanced the area under the concentration-time curve (AUC), prevented abrupt release, and raised the average dwell duration by more than six times while achieving sustained drug concentrations in plasma. The creation of long-acting transdermal drug delivery systems is aided by HP-PSA's excellent drug loading efficiency and regulated drug release capabilities. In order to deliver non-steroidal anti-inflammatory drugs (NSAIDs), researchers also created a high-capacity, high-release transdermal patch using COOH polyacrylate polymer (PA-1). This showed that ion-ion repulsion by decreasing hydrogen bonding can be a practical method of creating large-capacity, high-emission patches.^27,28

Utilisation of transdermal delivery methods in pain management²⁹

· Acute pain:

Nowadays, a wide range of patient groups and pain treatment specialties employ transdermal analgesics. The pain relief patch serves two purposes in the treatment and prevention of acute pain. An area of anesthesia is created by using a local anesthetic patch, for instance, to lessen the discomfort associated with vaccination or venesection. These patches are very helpful when working with children. Patches containing non-steroidal anti-inflammatory medications (NSAIDs) can be used to relieve acute pain from musculoskeletal injuries. Despite being used for many years, transdermal administration of opioids has not been advised for the treatment of acute pain because of the concerns of toxicity and delayed start of effect. The benefits of patient-controlled analgesia (PCA) combined with a transdermal administration method are combined in the fentanyl patient controlled transdermal system. It accelerates medication administration by an iontophoretic mechanism.

· Chronic pain:

Chronic nociceptive pain may benefit from the use of transdermal medications. For many years, patches containing fentanyl and buprenorphine have been accessible. For the treatment of persistent neuropathic pain, localized transdermal distribution of medications, such as topical lidocaine and capsaicin patches, may be beneficial.

· NSAID Patches:

The Voltarol gel patch with 1% Diclofenacepolamine is the only NSAID patch that is sold in the UK. It has a license to treat ankle sprains and epicondylitis locally. Topical NSAIDs are designed to enter the subcutaneous tissues and build up underneath the application site.

· Opioid Patches:

The m-agonist fentanyl and the partial m-agonist buprenorphine both have high lipid solubility and a low molecular weight making them well suited to being delivered transdermally.

· Fentanyl Patches:

Fentanyl used transdermally has a license to relieve both cancerous and non-cancerous pain. For drug distribution, manufacturers have employed both matrix and reservoir designs. For instance, "Mezolar" and "Osmanil" use the matrix design, while "Fentalis" and "Tilofyl" are reservoir patches. Matrifen features a rate-controlling membrane and a silicone drug-containing matrix. Fentanyl has been dissolved in an adhesive matrix found in the patented Durogesic D-Trans.³⁰

· Buprenorphine Patches:

The baine is the source of the potent opioid buprenorphine. There are two types of patches that employ a matrix design: the 96-hour Transtecw patch and the 7-day Butransw patch.³¹

· Fentanyl HCl Iontophoretic Transdermal System:

The only transdermal opioid that can be used to treat acute pain is the fentanyl HCl iontophoretic transdermal system (Fentanyl ITS), which is authorized for patient-controlled treatment of moderate-to-severe postoperative pain in a hospital setting.³²

· Local Anaesthetic Patches:

Venipuncture discomfort has been lessened using topical local anesthetics. Versatis (5%), a topical lidocaine patch, has been used more recently to treat the symptoms of neuropathic pain linked to post-herpetic neuralgia. With few systemic effects, the patch acts directly locally.

Other Advance Applications for Transdermal Patches:

Transdermal Vaccination Patches:

Transdermal patches are being developed by researchers as a more convenient and painless vaccination administration method than injections. Antibody neutralization and an increase in IFN-secreting cells have been demonstrated benefits of microneedle-based smallpox and influenza patches. With their enhanced immunogenicity and safer, easier immunization process, these patches have the potential to raise vaccination rates. This novel method may prove to be a viable substitute for conventional injections.^33,34

Transdermal Patches for Gene Therapy:

Gene therapy using transdermal patches to transfer genetic material to cancer cells has been investigated. A two-step casting process was used to create these patches, which were co-loaded with p53 DNA and IR820. The patches released p53 DNA and IR820 to subcutaneous tumor locations after effectively penetrating the stratum corneum and dissolving quickly. In vivo, the combination of gene therapy with photothermal agents showed a strong anti-tumor impact, suggesting that transdermal patches may be a viable method for treating subcutaneous tumors.³⁵

Transdermal Patches for Insulin Administration:

By transferring insulin through the skin and into the bloodstream, transdermal insulin delivery patches help diabetics. These patches, which are usually placed on the thigh, upper arm, or belly, emit a steady quantity of insulin over a certain amount of time. Researchers have created a novel method that enables the long-term release of loaded proteins by employing a water-swellable spherical double-layered microneedle (MN) patch at the tip. According to research on animals, swollen MN patches cause a delayed release of insulin, which gradually lowers blood glucose levels. To maximize these products' effectiveness and safety, more study is required.³⁶

In the Treatment of Cardiovascular Diseases- Transdermal Patches:

Decreased cardiac fraction of ejection and decreased drug metabolism are two consequences of heart failure's ability to change pharmacokinetics and pharmacodynamics. Transdermal patch administration devices are a feasible remedy since this may hinder medication absorption. For instance, when given orally, the nonselective beta-adrenergic blocker propranolol has a high hepatic first-pass metabolism. After an initial lag time of 8hours, the steady-state plasma concentration (Css) of transdermal patches is 9.3ng/mL, indicating a greater bioavailability. Atrial fibrillation, premature ventricular contraction, orthostatic hypotension, and aortic dissection have all been treated using Bisono® Tape, a transdermal patch containing bisoprolol as the active component. There is no change in Cmax between oral and transdermal clonidine, an antihypertensive medication that has been created for transdermal patch administration. Another medication being explored for transdermal administration is losartan, an angiotensin II receptor blocker. A medication used in cardiovascular treatment called nitroglycerin has been created for transdermal patch administration.³⁷

Transdermal Patches for Hormonal Deficiencies and Contraception:

Since 1938, there has been interest in transdermal hormone administration; the first transdermal patch for estradiol was released in 1984. A transdermal matrix delivery technology was used to create Menorest®, which has a superior pharmacokinetic profile, less variation in plasma estradiol, and greater local tolerability. In 2001, ethinylestradiol—a mix of ethinyl estradiol and norelgestromin—was authorized as the first transdermal ethinyl estradiol contraceptive. Male hypogonadism has also been treated with testosterone using a variety of techniques, such as transdermal testosterone patches and intravenous testosterone enanthate. Whereas reservoir testosterone transdermal patches, such as Androderm, have a Cmax of 765 ng/L with a mean Tmax of 8 hours at 16 weeks, intravenous treatment produces a Cmax of nearly 1200ng/L 24 hours after the injection.³⁸

Transdermal Patches for the Treatment of Disorders of the Central Nervous System (CNS):

The development of transdermal drug delivery systems for medications pertaining to the central nervous system has benefits. It offers long-term therapeutic dosage at plasma levels, to start. Second, the transdermal drug delivery method demonstrated a good absorption and pharmacological profile. Third, it reduces systemic side effects since patients tolerate it well.³⁹

CONCLUSION:

This study examined the transformational potential of transdermal drug delivery systems (TDDS) as a contemporary, non-invasive method for drug administration. These solutions provide exceptional effectiveness while alleviating the discomfort sometimes linked to conventional treatments, such as injections. Through the use of technological breakthroughs, TDDS are set to transform medicine distribution, providing more convenience, enhanced patient adherence, and improved therapeutic results. As the field progresses, TDDS leads in innovation, streamlining drug delivery and enhancing the entire patient experience.

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Received on 17.01.2025 Revised on 06.04.2025

Accepted on 11.06.2025 Published on 08.07.2025

Available online from July 12, 2025

Asian J. Pharm. Tech. 2025; 15(3):305-311.

DOI: 10.52711/2231-5713.2025.00046

This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License. Creative Commons License.

Type	Structure	Use	Material	Dose	Delivery Rate	Ref.
Coated	Complex	Single	Polymer, Sugar, Lipid	More Precise Dosing	Fast	^9,10
Hollow/ Hydrogel	Simple	Can be reuse	Silicon	Large Dose	Fast	^11,12,13,14
Solid	Simple	Can be reuse	Silicon, Metal, Polymer	Small Dose	Fast	^15,16,17
Dissolving	Complex	Single	Polymer	More Precise Dosing	Slow	^18,19,20,21