Lecture 21 Transdermal delivery

Question 1

Describe the role of the skin as an organ in the human body, including its size, functions, and histological layers.

Answer 1

The skin is the largest organ in the human body, covering about 2 m2 and serving as a barrier against external influences. It regulates temperature, transmits sensory information, and consists of the epidermis, dermis, and subcutis.

Question 2

Explain the composition and functions of the stratum corneum in the epidermis.

Answer 2

The stratum corneum is a barrier layer in the epidermis made of lipophilic and hydrophilic cells. It contains water, protein (mainly keratin), and lipids, and serves as a rate-limiting barrier that continually sheds and replaces cells.

Question 3

Discuss the significance of skin appendages like hair follicles and sweat glands in human skin.

Answer 3

Human skin contains hair follicles and sweat glands that play roles in temperature regulation and sebum secretion. While not significant for drug delivery, they are essential for bodily functions.

Question 4

How does the skin contribute to maintaining internal body temperature and protecting against external influences?

Answer 4

The skin helps regulate body temperature by controlling water loss and acts as a barrier against harmful molecules and microorganisms. It also transmits sensory information to the central nervous system.

Question 5

Define the main histological layers of the skin and their respective functions.

Answer 5

The skin consists of the epidermis, dermis, and subcutis. The epidermis provides a protective barrier, the dermis contains blood vessels and nerves, and the subcutis serves as insulation and energy storage.

Question 6

Describe the composition and functions of sweat glands in human skin.

Answer 6

Sweat glands in human skin, including eccrine and apocrine glands, help regulate body temperature by producing sweat. Eccrine glands are universal, while apocrine glands are found in specific regions like the axillae and anogenital areas.

Question 7

Describe the main routes of skin transport and the components of the stratum corneum according to the ‘bricks and mortar’ model.

Answer 7

Skin transport can occur transepidermally via intact stratum corneum or transappendageally via hair follicles and sweat glands. The stratum corneum consists of fibrous protein networks (bricks/corneocytes) and an intercellular network of neutral lipids (mortar).

Question 8

How do the intercellular lipids in the stratum corneum contribute to drug permeation via the intercellular route?

Answer 8

The intercellular lipids in the stratum corneum, including ceramides, cholesterol, and free fatty acids, form alternating lipid bilayers with hydrophilic areas, creating aqueous channels. Lipophilic drugs pass through lipid bilayers, while hydrophilic drugs move through aqueous channels.

Question 9

Define the factors limiting transdermal drug delivery and the physicochemical properties required for successful delivery.

Answer 9

Transdermal drug delivery is limited to drugs with molecular mass < 600 Da, good solubility in oil and water, high SC:vehicle partition coefficient, and low melting point for better solubility.

Question 10

Explain the role of cholesterol in the stratum corneum and how it affects the barrier function of the skin.

Answer 10

Cholesterol in the stratum corneum imparts rigidity to the hydrophobic region, facilitating the mixing of lipid components. It plays a crucial role in maintaining the barrier function of the skin by contributing to the unique and highly organized lipid bilayer structure.

Question 11

Describe the movement of lipophilic and hydrophilic drugs through the stratum corneum during transdermal drug delivery.

Answer 11

Lipophilic drugs move through the lipid bilayers of the stratum corneum, while hydrophilic drugs follow a polar route through the aqueous channels between the bilayers. This differential movement influences drug permeation and absorption.

Question 12

How do penetration enhancers, increased temperature, and hydration affect the lipid fluidization in the stratum corneum during drug permeation?

Answer 12

Penetration enhancers, increased temperature, and hydration can act on the stratum corneum to fluidize lipids, enhancing drug permeation. They target the intercellular lipids, promoting fluidization and facilitating drug transport through the skin barrier.

Question 13

Describe the components of the cutaneous absorption resistance model and how the chemical magnitude of a barrier membrane resistor to drug diffusion is expressed.

Answer 13

The percutaneous absorption resistance model includes R1 (vehicle resistance), R2 (appendageal resistance), R3 (stratum corneum resistance), and R4 (viable tissue resistance). The chemical magnitude (R) is expressed as R = h/Fsc.Dsc.Ksc, where h = thickness, Fsc = fractional area, Dsc = drug diffusion coefficient, and Ksc = tissue capacity for drug.

Question 14

How does the percutaneous absorption resistance model differentiate between transappendageal resistance, stratum corneum resistance, and viable tissue resistance?

Answer 14

The model distinguishes between transappendageal resistance, which has low fractional area, stratum corneum resistance, and viable tissue resistance from the viable epidermis and dermis. The transappendageal route has a low fractional area, while resistance due to the dermis is negligible compared to the stratum corneum.

Question 15

Define the formulation strategy in the context of percutaneous absorption.

Answer 15

The formulation strategy in percutaneous absorption involves considering the components of the resistance model (R = h/Fsc.Dsc.Ksc) to optimize drug delivery through the skin barrier. It focuses on factors like thickness, fractional area, drug diffusion coefficient, and tissue capacity for drug to enhance drug absorption.

Question 16

How is the chemical magnitude of a barrier membrane resistor to drug diffusion calculated in the percutaneous absorption resistance model?

Answer 16

The chemical magnitude (R) is calculated as R = h/Fsc.Dsc.Ksc, where h represents the thickness of the resistor membrane, Fsc is the fractional area of the route, Dsc is the drug diffusion coefficient through the resistor, and Ksc is the tissue capacity for drug (tissue/vehicle partition coefficient). This calculation helps understand the resistance to drug diffusion through the skin barrier.

Question 17

Describe the significance of the stratum corneum resistance in the percutaneous absorption resistance model.

Answer 17

The stratum corneum resistance plays a crucial role in the percutaneous absorption resistance model as it represents a major barrier to drug diffusion. Its resistance value (R3) impacts the overall chemical magnitude of the barrier membrane resistor to drug diffusion, influencing the effectiveness of drug delivery through the skin barrier.

Question 18

Describe the concept of lag in percutaneous drug absorption in vivo and how it is related to membrane thickness and drug diffusion coefficient.

Answer 18

In percutaneous drug absorption, the lag time (tl) is the time before steady state diffusion is established, determined by membrane thickness (h) and drug diffusion (D) through the membrane (tl = h2/6D). It can be calculated from the penetration profile, with the shortest lag time for transappendageal route and longest for transepidermal pathway.

Question 19

What are the factors that affect percutaneous absorption, both related to the skin and the drug itself?

Answer 19

Skin factors influencing percutaneous absorption include skin health, hydration, occlusion, age, binding, regional variation, ethnicity, and temperature.
Drug factors include concentration, partition coefficient, ionisation degree, solubility, and chemical structure.

Question 20

Explain the characteristics and mechanism of a matrix drug-in-adhesive transdermal patch system.

Answer 20

A matrix drug-in-adhesive transdermal patch system involves diffusion-controlled drug release with a drug in a polymer matrix surrounded by adhesive or dispersed in the adhesive layer. It exhibits a non-constant release rate and cumulative release amount following a square root time dependency (Q ∝ t^0.5).

Question 21

Define the concept of steady state diffusion in percutaneous drug absorption and discuss its relevance in drug delivery processes.

Answer 21

Steady state diffusion in percutaneous drug absorption refers to a state where the rate of drug absorption equals the rate of drug elimination, ensuring a constant drug concentration. In drug delivery processes, achieving steady state diffusion is crucial for maintaining consistent drug levels.

Question 22

How does Fick’s second law of diffusion play a role in modeling percutaneous drug absorption in vivo, especially in non-steady state conditions?

Answer 22

In non-steady state percutaneous drug absorption, Fick’s second law of diffusion provides a more rigorous model to understand the process. It helps in determining factors like lag time, membrane thickness, and drug diffusion coefficient, essential for drug delivery optimization.

Question 23

Describe the structure and function a matrix dispersion-type transdermal patch with a drug reservoir and a rate-controlling membrane.

Answer 23

A matrix dispersion-type transdermal patch consists of a drug reservoir where the drug is dispersed in solid polymer, suspended in viscous liquid, or dissolved in solvent. It also includes a rate-controlling membrane, such as EVA, to ensure constant release rate. This type of patch is a zero-order (controlled release) device.

Question 24

How are in-vitro methods, specifically the Franz diffusion cell, utilized in the evaluation of transdermal patches?

Answer 24

In-vitro methods, like the Franz diffusion cell, are used to assess transdermal patches by measuring the cumulative amount of drug penetrating the membrane over time. This method helps determine the release rate and efficiency of drug delivery through the skin.

Question 25

Define the concept of a transdermal patch with a drug reservoir and explain how the drug release is controlled in such a system.

Answer 25

A transdermal patch with a drug reservoir contains a solid polymer where the drug is dispersed, suspended in a viscous liquid, or dissolved in a solvent. The drug release is controlled by a rate-controlling membrane, like EVA, ensuring a constant release rate.

Question 26

What are the key components of a transdermal patch with a drug reservoir, and how does the reservoir contribute to drug delivery through the skin?

Answer 26

The key components include a drug reservoir where the drug is dispersed in solid polymer, suspended in viscous liquid, or dissolved in solvent. The reservoir plays a crucial role in controlling drug release and facilitating delivery through the skin.

Question 27

Describe the mechanism of drug release in a transdermal patch with a drug reservoir and a rate-controlling membrane.

Answer 27

In a transdermal patch with a drug reservoir, drug release is controlled by the rate-controlling membrane, such as EVA, ensuring a constant release rate. The drug is typically dispersed in solid polymer, suspended in viscous liquid, or dissolved in a solvent within the reservoir.