A "drug delivery system" (DDS) is any of a number of sophisticated physicochemical techniques intended to optimize the therapeutic potential of pharmacologically active substances by controlling their release and distribution inside cells, tissues, and organs. DDS focuses on the formulation and administration techniques that effectively transport drugs in order to maximize treatment effectiveness and reduce side effects. There are numerous methods of administration, each with a distinct delivery mechanism, including mucosal, intravenous, transdermal, lung inhalation, and oral. The transdermal drug delivery system (TDDS) is one of these that has drawn a lot of interest as a very promising tactic. Contrary to traditional direct administration techniques, which usually entail injections using needles, transdermal drug delivery via skin (TDDS) has become a well-researched non-invasive alternative. Significant effects of TDDS have been seen in the distribution of many medicinal drugs, including those used to treat pain management, hormone therapy, and illnesses of the central nervous system and heart. By avoiding the digestive tract, TDDS guarantees that first-pass metabolism does not result in loss and that medications can be delivered without interference from intestinal flora, pH, or enzymes. The ability of TDDS to regulate drug release in accordance with usage restrictions and its non-invasive design are other factors contributing to its appeal.  Scopolamine was the medication used in the first transdermal drug delivery (TDD) system, Transderm-Scop, which was created in 1980 to treat motion sickness. The transdermal device is a system that is membrane-moderated. In this technology, a microporous polypropylene sheet serves as the membrane. The medication is dissolved in a blend of mineral oil and polyisobutylene to form the drug reservoir. This research release is sustained for a duration of three days. The innovative drug delivery method for currently available pharmacological compounds has attracted increasing attention recently. In addition to increasing a medicine's safety and effectiveness, the innovative drug delivery method also boosts patient compliance. Transdermal drug delivery systems (TDDS) are discrete dose forms that are self-contained. Another benefit of the TDDS is that the dosage is lower than with the oral medication delivery method.

Advantages of transdermal drug delivery system: -

1. One can lower the dose frequency.
2. Because of increased bioavailability, drug concentration can be decreased.
3. It is possible to avoid the liver's first pass metabolism.
4. They can avoid problems with gastrointestinal medicine absorption brought on by enzymatic activity, stomach pH, and drug interactions with food, beverages, and other oral medications.
5. Lower drug side effects and decreased plasma concentration levels of the medications.
6. Because they are non-invasive, they eliminate the inconvenience of parenteral therapy.
7. Because they provided prolonged therapy with a single application, they increased compliance in comparison to earlier dosage forms that necessitated more frequent dose administration.
8. Drug therapy can be quickly stopped by removing the application from the skin's surface.
9. With these systems, self-administration is feasible.
10. It lessens drug interactions across the board.
11. It provides a longer action duration.

Disadvantages of transdermal drug delivery system: -

1. The medicine needs to have certain desirable physicochemical qualities in order to penetrate the stratum cornea. Transdermal delivery will be extremely challenging if the drug dose needed for therapeutic value exceeds 10 mg/day.
2. Due to the skin's natural barriers to drug entrance, only somewhat powerful medications are appropriate candidates for TDDS.
3. Some patients require stopping treatment because they get contact dermatitis at the application site for one or more system components.
4. Another aspect that must be thoroughly considered before deciding to manufacture a transdermal medicine is clinical need.
5. The skin's barrier function varies with age, from person to person, and from one place to another on the same individual.

Limitation of transdermal drug delivery system: -

1. Low permeability of the skin
2. Limited to strong medications
3. Unsuitable for molecules larger than 500 Daltons
4. The patch's adhesion to the skin 5. The drug's potential for skin degradation
5. Because highly melting drugs are little soluble in fat and water, they cannot be administered via this method.
6. If they irritate the skin, they are completely inappropriate.
7. Ionic medications cannot be delivered by this technology.

An ideal drug candidate for transdermal drug delivery should require the following characteristics.  

1. The molecular weight ought to be under 500 Da.

2. A log partition coefficient that is ideally between one and three

3. Strong chemical; fewer than ten milligrams.

4. The solubility in water should be more than 100 ug/ml.

Types of TDDS:

Transdermal Patch:

The application of a medicated adhesive patch to the skin allows for the controlled delivery of a prescribed dosage of medication via the skin and into the bloodstream, resulting in a therapeutic effect.

       
           
       
Advantages of Transdermal drug delivery System

• Reducing the frequency of doses.
• Increased bioavailability can lead to a decrease in medication concentration.
• The liver's first pass metabolism can be circumvented.
• They can avoid problems with gastrointestinal medicine absorption brought on by enzyme activity, stomach pH, and drug interactions with food, beverages, and other oral medications.
• Lower drug side effects and decreased plasma concentration levels of the medications.
• Because they are non-invasive, they spare users from the inconvenience of parenteral therapy.
• Because they provided prolonged therapy with a single application, they increased compliance in comparison to earlier dosage forms that necessitated more frequent dose administration.
• These methods allow for self-administration;
• Drug therapy can be stopped quickly by removing the application from the skin's surface.
• It lessens drug interactions across the board.
• It provides a longer action duration.

Disadvantage of Transdermal Drug Delivery System:

• Transdermal administration is appropriate only for strong medications.
• This technique is not cost-effective; some patients may experience skin irritation at the application location.
• Dosage dumping may occur if the medication binds to the skin.
• Only chronic illnesses, such as diabetes, hypertension, angina, and so on, should be treated with it; acute conditions should not be treated with it.
• Cutaneous metabolism may have an impact on the medication's therapeutic effectiveness.
• Transdermal treatment is not appropriate for ionic medications.
• Fit for medications with smaller molecular weights, meaning fewer than 500 Daltons

Anatomy and physiology of Skin:

With a total size of almost 20 square feet, the skin is the biggest organ in the body. In addition to helping to regulate body temperature and shielding us from germs and the environment, skin also allows us to feel touch, heat, and cold.

Epidermis: Keratinocytes, which create the protein keratin, make up the majority of the epidermis, the skin's outermost layer. This layer establishes our skin tone and acts as a waterproof barrier. The stratum corneum, stratum lucidum, stratum granulosum, stratum spinosum, and stratum basale are among the sub-layers that make up the epidermis.

Dermis: Underneath the epidermis, the dermis is the middle layer of skin. It is made up of nerve endings, sweat glands, hair follicles, blood vessels, and connective tissue. The skin's dermis gives it flexibility, nutrients, and structural stability. The dermis is composed of two sub-layers: the reticular dermis and the papillary dermis..

Adipose tissue, or fat, and connective tissue make up the hypodermis, or subcutaneous layer, which is the innermost layer. This layer gives the body comfort, insulation, and energy storage. Additionally, it fixes the skin to the underlying bones and muscles. The skin also contains a variety of specialized cells and structures in addition to these major layers, including melanocytes (which are in charge of skin color), Langerhans cells (which control the immune system), and Merkel cells (which control feeling). The skin's intricate structure allows it to protect the body in an efficient manner while still performing vital tasks.

Types of Transdermal Patches

Single layer drug in adhesive:

This kind has the medication embedded in the sticky layer. The medicine is released into the skin via the adhesive layer, which also acts as a glue to hold the other layers together. There is a backing and a temporary liner surrounding the adhesive layer.

       
           
       
Multi-layer drug in adhesive:

       
           
       
Figure 2 Multilayer patch

It is distinguished by the presence of a liquid compartment with a medication solution or suspension that is kept apart from the release liner by an adhesive and semi-permeable membrane. The adhesive component of the product that is in charge of skin adhesion can be included in either a concentric design surrounding the membrane or a continuous layer between the membrane and the release liner.

       
           
       
Drug Matrix-in-Adhesive:

It is distinguished by the presence of a semisolid matrix that is in direct contact with the release liner and contains a medication solution or suspension. The skin-adhering component is integrated into an overlay and surrounds the semisolid matrix in a circular pattern.

This kind of patch uses an adhesive layer that releases vapour in addition to holding the different layers together.  The newest products on the market are vapor patches, which release essential oils for as long as six hours. Vapour patches, which release essential oils for up to 6 hours, are just now beginning to appear on the market. The vapor patches release essential oils and are mostly used to treat cases of congestion. As an alternative, controller vapour patches are available that improve the quality of sleep. Additionally, there are vapour patches available that help reduce the number of cigarettes a person smokes each month. Month can also be found in the market.

Different Transdermal Drug Delivery Technologies:

By using targeted heat to deliberately disturb the stratum corneum structure, thermal ablation, sometimes referred to as thermophoresis, is a promising technique that improves medication administration by creating microchannels in the skin. In order to thermally ablate the stratum corneum, a temperature well above 100 °C is necessary, which causes keratin to heat up and vaporize. Furthermore, the degree of the stratum corneum structure alteration is directly related to the locally elevated temperature, suggesting that this technique is perfect for accurate drug delivery management. Depending on the various sources of thermal energy, laser and radiofrequency techniques can typically generate thermal ablation.

Thermal ablation techniques use a laser to create the skin's micropore structure and raise the skin's temperature, which raises the diffusivity of the skin. Water excitation and explosive evaporation from the epidermis result from laser light energy being absorbed by skin pigments and water, which then turns into heat energy. Many parameters, including wavelength, pulse length, energy, number and repetition rate, tissue thickness, absorption coefficient, and laser exposure duration, can be carefully adjusted to determine the degree of ablated skin depth.

       
           
       
Fig- Thermal ablation

A needle is used in the microneedle drug delivery system, a revolutionary drug delivery method, to administer medication to the circulatory system. This is a popular approach of transdermal drug delivery and a topic of ongoing research at the moment. This approach includes puncturing the skin's superficial layer with needles the size of microns, which diffuses the medicine throughout the epidermal layer. These short, thin microneedles carry medications directly to the blood capillary area for active absorption, reducing the risk of pain.

       
           
       
Fig- microneedle drug delivery

Researchers have endeavored to employ several methodologies to achieve the suitable optimization and geometric measurements necessary for the successful insertion of microneedles into human skin, which also signifies the overarching goal of microneedle research. Usually arranged on a single side of a supporting base or patch, MN are numerous tiny projections with dimensions typically between 25 and 2000 ?m in height, 50 to 250 ?m in base width, and 1 to 25 ?m in tip diameter. When implanted into layers of skin, the needles should have the proper length, breadth, and form to prevent contact with nerves. Typically, they are arranged in arrays to enhance the skin's surface contact and promote the skin's absorption of medicinal chemicals.

JET injector

The liquid is propelled by liquid-jet injectors through nozzles with orifice diameters varying from 50 to 360 ?m. This is significantly less than the usual hypodermic needle's outer diameter of 810 ?m for a 21G needle.

By adjusting the jet velocity and orifice diameter, the jet can transport a medicine into the intradermal (i.d.), subcutaneous (s.c.), or intramuscular (i.m.) layers of skin.The primary benefit of utilizing needle-free gadgets pertains to worries about secure needle disposal and preventing unintentional injuries from needle sticks. Cross-contamination is still possible, though, as the nozzle could get contaminated by interstitial liquid that splashes back from the skin. Consequently, the usage of multi-use nozzle jet injectors has been discontinued, and certain devices—like the Tjet® device, which distributes somatropin (human growth hormone (hGH))—are now limited to administering multiple doses of medication to the same patient.

       
           
       
Fig -T-jet

Compressed gas is used as the power source in solid jet injectors, which also have a drug-loaded chamber with a solid drug formulation and a nozzle to direct the particle flow towards the skin. Compressed gas expands when the actuation mechanism is activated, pushing medication powder via a nozzle and into the skin. Particles strike the skin, producing microscopic holes that settle in the viable epidermis or stratum corneum. Particle qualities (size, density, and impact velocity) are the most crucial factors that control particle distribution through the stratum corneum. For example, the particle size range for DNA vaccine should be between 0.5 and 3 µ.