Transdermal Delivery Disadvantages

1. Transdermal delivery: Transdermal delivery of drugs is a convenient route of administration for a variety of clinical indications. Transdermal delivery has many advantages over the conventional drug delivery 1, 2, 3. Transdermal delivery faces significant barrier across the skin, associated mainly with outermost stratum corneum layer of epidermis which limits it to fewer drugs 4, 5. The skin structure consists of stratum corneum cells are embedded within intercellular lipid lamellae 6. These lamellae are also responsible for imparting barrier properties to the stratum corneum 7, 8. As a result, very less quantity (mg) of drug can be delivered by this route. This limits its application to only potent drugs. Work is going on to overcome

• It can target the gastrointestinal system drug that degrades by the acid and enzymes present in it.
• Transdermal administration avoids first pass metabolism.
• It allows continuation of drug administration with short biological half-life.
1.2.2 Disadvantages of TDDS9
• One of the greatest disadvantages to transdermal drug delivery is the possibility of local irritation that may develop at the site of application.
• In patch formulation, the drug, the adhesive, or other excipients, can cause erythema, itching and local edema. For most patients, changing site can minimize irritation.
• The skin’s low permeability limits its use for fewer drugs.
• Many drugs with a hydrophilic structure permeate the skin too slowly resulting in no therapeutic benefit.

1.3 Skin: The skin is very extensive and easily accessible organ of the human body. The skin of human being covers an average area of about 2m2, weighs 4.5-5 kg (about 16 % of total body weight). It is supplied by 1/3rd of the total blood supply. The human skin thickness ranges from 0.5 mm (on the eyelids) to 4 mm (on the

Blood vessel
2. Lymph vessel
3. Sensory nerve ending
4. Sweat glands and their ducts
5. Hair roots, hair follicles and hairs
6. Sebaceous gland
The dermis is structurally divided into two main areas: a superficial area (adjacent to the epidermis), called the papillary region, and a deep thicker area known as the reticular region10, 11.

Papillary region: The papillary region is composed of loose areolar connective tissue. It is named after its fingerlike projections called papillae which extend toward the epidermis. The papillae projecting into the epidermis in the palms, fingers, soles, and toes, forms contours in the skin's surface, which are called friction ridges. Friction ridges are unique to all individual due to their occurring pattern. These patterns are genetically and epigenetically determined, making the use of fingerprints or footprints as a means of identification12.

Reticular region: The reticular region is much thicker than the papillary region. It lies deep down in the papillary region. It comprises of dense irregular-connective tissue. It is named after the dense concentration of collagenous, elastic, reticular fibers that weave throughout it. These protein fibers, provides strength, extensibility and elasticity to the dermis. The roots of hair, sebaceous glands, sweat glands, receptors, nails, and blood vessels are also located in the reticular