Introduction to Transdermal drug delivery system.


Introduction.

  • Transdermal drug delivery systems (TDDS), also known as "patches," are dosage forms that are designed to deliver a therapeutically effective amount of drug through the skin of a patient. 

  • TDD is a painless method of systemic drug delivery that involves applying a drug formulation to intact and healthy skin. 

  • The drug penetrates the stratum corneum first, then the deeper epidermis and dermis, with no drug accumulation in the dermal layer

  • When a drug enters the dermal layer, it is available for systemic absorption through the dermal microcirculation. 

  • Transdermal delivery outperforms injectables and oral routes by increasing patient compliance and avoiding first pass metabolism

  • Transdermal delivery not only provides controlled, consistent drug administration, but also allows continuous input of drugs with short biological half-lives and eliminates pulsed entry into systemic circulation, which frequently causes undesirable side effects.

Advantages of TDDS:

Disadvantages of TDDS:

Anatomy of Skin:

Epidermis: 

  • Stratified, squamous, keratinizing epithelium. 

  • Keratinocytes are the most abundant cellular component (> 90%) and are in charge of the evolution of barrier function. 

  • When keratinocytes migrate to the skin's surface, they change shape, size, and physical properties. 

  • The epidermis is further divided into five anatomical layers, each approximately 100-150 micrometers thick, with the Stratum corneum (SC) forming the epidermis's outermost layer, exposing it to the external environment. 

  • This is the most important layer in transdermal delivery because of its ability to keep water within the body and foreign substances out. 

  • SC is made up of dead cells that have migrated up from the stratum granulosum and are large, flat, polyhedral, plate-like envelopes filled with keratin. 

  • The SC is made up of 10-15 layers of corneocytes that range in thickness from 10-15 m in the dry state to 40 m when hydrated. 

Dermis: 

  • The dermis is made up of an extensive microvascular network of structures such as sweat glands, hair follicles, and smaller blood vessels. 

  • To achieve drug delivery through the skin, the drug must first pass through the epidermis and into the dermis, where it can be absorbed by capillaries into the circulatory system. 

  • The inner and larger (90%) skin layer is made up primarily of connective tissue and serves to support the skin's epidermis layer. 

  • The Dermal-Epidermal junction is the boundary between the dermis and epidermis layers, and it serves as a physical barrier for large molecules of drug and cells. 

  • It contains blood and lymphatic vesicles, as well as nerve endings

  • Dermis can be divided into two anatomical region; 

    • papillary dermis and 

    • reticular dermis

  • Papillary dermis is the dermis's thin outermost layer. 

  • Collagen and elastin fibers are mostly vertically oriented and connect with the dermal-epidermal junction in the papillary region. 

Hypodermis

  • The subcutaneous layer, additionally called the hypodermis in histology, is the 3 layers below the dermis. 

  • The subcutaneous layer is an elastic layer that includes a massive range of fat cells that act as a shock absorber for blood vessels and nerve endings. 

  • This layer has an average thickness of four to 9 mm. 

  • The real thickness, however, varies from individual to individual and depends on the body region. 

  • While a molecule enters intact skin, it comes into touch with cell particles, normal flora of microorganisms, sebum, and different substances.

Routes of skin penetration.

  • Transcellular transport is the primary mode of transport for water-soluble molecules. 

  • It entails the passage of corneocytes through their cytoplasm and the lipid arrangement of the stratum corneum. 

  • The transport pathway for lipid soluble molecules is intercellular; it appears to involve passage through endogenous lipids within the stratum corneum. 

  • The transcellular and intercellular routes are referred to collectively as the trans-epidermal route, as shown below. 

  • Solute molecules may penetrate the skin through the hair follicles, sweat duct or through the sebaceous glands. These passages are collectively known as shunt or appendageal route. 

  • It is generally accepted that the skin appendages comprise approximately 0.1% of fractional area for drug permeation. 

  • Thus, the main focus is to develop permeation strategies through the stratum corneum rather than through the appendages. 

  • The dead cells of the SC, which restrict the inward and outward movement of drug substances and have a high electrical resistance, are the main barriers to absorption. 

  • The SC is a heterogeneous tissue made up of flattened keratinized cells. 

  • These cells' outer layers are less densely packed than the underlying granular layer. 

  • As a result, the lower part of the epidermal barrier becomes more impermeable. 

  • As molecules move from the environment into the skin, the SC serves as the rate limiting barrier, or the tissue that provides the greatest resistance to the movement of molecules. 

  • After applying the dosage form topically, the percutaneous absorption or transdermal permeation can be visualized as a series of steps. 

    • a. Adsorption of a penetrant molecule onto SC surface layers 

    • b. Diffusion through the SC and viable epidermis.

Percutaneous Absorption

  • It is a three-part process that involves the gradual penetration of substances into different skin layers and their permeation through the skin into systemic circulations: 

    • The entrance of a substance into a specific layer is known as penetration. 

    • Permeation: the transition from one layer to another, which differs from the first layer in terms of both function and structure.

    • Absorption: the process of a substance entering the bloodstream. 

Commonly Asked Questions.

  1. What is a Transdermal Drug delivery system? Write a short note on Anatomy of the human skin.

  2. What is a Transdermal Drug delivery system? Discuss different routes from which drug gets absorbed through the skin.

  3. What is a Transdermal Drug delivery system? Give its advantages and disadvantages.

  4. Write a short note on Stratum corneum and its importance in TDDS.

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