Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

PHRM 100 – PDD > PDD 12: Semi-Solid Dosage Forms – Skin and Dermal Drug Delivery > Flashcards

PDD 12: Semi-Solid Dosage Forms – Skin and Dermal Drug Delivery Flashcards

1
Q

What are the 2 types of skin?

A
  • hairy skin
  • glabrous skin
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What is hairy skin?

A

hair follicles + sebaceous glands

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What is glabrous skin?

A

soles of palms and feet

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What are the 3 layers of human skin?

A
  • epidermis
  • dermis
  • subcutis (hypodermis)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What do skin cells (keratinocytes) produce?

A

produce keratin, which gives strength against mechanical stress

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What is the epidermis?

A

4-5 layers, depending on anatomical region

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Epidermis

What is the most important layer to topical drug delivery?

A

stratum corneum (horny layer)

  • dense tissue of compressed keratin filled corneocytes anchored in a lipophilic matrix of lipids (ceramides, free fatty acids, cholesterol)
  • stratum corneum is about 15-25 cells deep (10-15 μm), epidermis about 10x larger
  • this layer is continuously sloughed off and replaced with complete turnover of about 2 week
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What is viable epidermis?

A

multilayered region of cells undergoing various stages of differentiation

  • stratum basale layer is the bottom layer – a single layer of constantly dividing cells moving upwards to replace the stratum corneum
  • as cells move upwards they differentiate and change morphology (become flattened)
  • extends into the subcutaneous regions via the hair follicle
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What is the dermis?

A

fibrous layer that supports and
strengthens the epidermis

  • dense network of structural collagen and elastin fibres embedded in a ground substance of water, ions, proteoglycans
  • consists of microcirculatory vessels, sensory nerves, lymphatics, sebaceous glands (secrete sebum) and sweat glands (secrete sweat)
  • capillaries do not enter the epidermis
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

What is hypodermis?

A

deepest layer of the skin, essential component of the skin’s structure

  • composed of adipose tissue, loose connective tissue, and blood vessels
  • also referred to as subcutaneous layer or subcutis
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What is the skin?

A

largest organ with regenerative ability

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What is the function of skin?

A

primary function: act as a flexible “container” for body fluids and tissues

  • protects the body from chemical, physical and microbiological attacks
  • maintains and regulates body temperature, mediates sensations (heat, cold, touch, pain), produces vitamin D
  • identifies individuals (colour, hair, odour and texture)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What are dermal drug delivery systems?

A

drug incorporated into a system such as a cream, ointment, paste, lotion, gel which are applied to the skin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What is dermal drug delivery?

A

intended for a localized effect with no or minimal systemic uptake/absorption to:

  • manipulate the barrier function of the skin
  • direct drugs to the viable skin tissues without using systemic administration
  • in general, systemic drug levels are low and systemic pharmacological effects should be negligible
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What is transdermal drug delivery?

A

delivery of drugs through the skin and into the systemic circulation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

What are the target sites for dermal drug delivery? (4)

A
  • skin surface
  • stratum corneum
  • viable epidermis and dermis
  • skin appendages
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

Why do dermal formulations act at the surface of the skin? (4)

A
  • protective or barrier effect: sunscreens, barrier products (prevent moisture loss, prevent contact of urine with skin)
  • cosmetic: cover blemishes, birthmarks, scars
  • cleansing and antiseptic products: reduce or prevent growth of skin surface microflora in cuts and abrasions
  • deodorants: target the skin surface to keep microbial growth in check and to prevent or slow the rancidification of secretions of sweat glands
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

Why do dermal formulations act on the stratum corneum? (2)

A
  • emolliency
  • keratolysis
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

What is emolliency?

A

softening of the horny layer of the skin by moisturizing it

  • water content of the stratum corneum is 15-20% of its dry weight but can hold up to 75% of its weight (ie. it can swell a lot)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

What is keratolysis?

A

removal of the thickened or scaly horny tissue

  • agents loosen keratin and slough off surface cell
21
Q

The viable epidermis and dermis layer of skin is targeted for the treatment of what? (5)

A
  • inflammation
  • pain (topical anesthetics)
  • infections (athletes foot, cold sores)
  • malignancies (moles, skin cancer)
  • scars
22
Q

What are skin appendages?

A

hair, arrector pili, sweat glands, sebaceous glands and nails

23
Q

Why are skin appendages targeted?

A

for certain conditions including:

  • acne or seborrhoea (sebaceous glands)
  • fungal conditions (nails and hair)
24
Q

What are the 2 drug transport processes?

A
  • passive diffusion – move across concentration gradient
  • partitioning – b/w one skin layer into the next
25
Q

What is the rate limiting barrier to drug penetration through the skin and why?

A

–

26
Q

What is percutaneous absorption?

A

transfer of a drug from the surface of the skin into the stratum corneum and the subsequent partitioning and diffusion through the stratum corneum, viable epidermis, dermis and eventual uptake into the microcirculation

27
Q

Pathways for Drug Transport Across the Striatum Corneum

What is the rate limiting barrier to percutaneous absorption?

A

stratum corneum has a very large surface area (99.9% of total skin area)

28
Q

Pathways for Drug Transport Across the Striatum Corneum

What are the 2 primary routes of transport?

A
  • transcellular: drugs diffuse through the keratin rich corneocytes / keratinocytes – drug diffuses through the “free volume” of the cell
  • intercellular: drugs diffuse between the cells – this intercellular matrix is rich in lipids and is an important route for penetration of many hydrophobic drugs
29
Q

Pathways for Drug Transport Across the Striatum Corneum

What is the brick and mortar model?

A

describes the stratum corneum

  • ‘bricks’ are corneocytes (I) and are surrounded by ‘mortar’ made of a bilayer of lipids (II) and water (III)
30
Q

Pathways for Drug Transport Across the Striatum Corneum

What is the transappendageal route?

A

only makes up ~0.1% of drug transport

  • may be useful for large polar molecules that have difficulty crossing the epidermis
31
Q

What type of drug transport occurs through the skin?

A

passive diffusion + partitioning

32
Q

What is passive diffusion?

A

molecular movement down a concentration gradient

  • speed at which a drug diffuses (ie. rate of diffusion) is proportional to concentration gradient
33
Q

What is partitioning?

A

movement of molecules form one phase to another

  • described by a partition coefficient
34
Q

What are the characteristics of drugs that make it suitable for transdermal delivery?

A
  • logP between 1 and 3 – highly lipophilic, better permeability
  • MW under 600 Da – smaller molecules, better permeability
  • high biological activity (< 10 mg/day) – low doses for therapeutic effect
  • and not cause skin irritation
35
Q

Drug Transport Through Skin

What are sink conditions?

A

C approaches 0 (ie. drug reaching viable layers is immediately removed so the concentration there is approximately 0, so C = 0)

  • rate of diffusion through stratum corneum is rate limiting
  • rate of diffusion through viable layers must be much greater
36
Q

Why is there a lag phase?

A

–

37
Q

What factors influence percutaneous absorption?

A

biological factors:

  • skin condition
  • skin age
  • regional skin sites
  • skin hydration and occlusion

physicochemical factors:

  • partition co-efficient
  • drug concentration and solubility
  • penetration enhancers
38
Q

Biological Factors Affecting Percutaneous Absorption

Skin Conditions

A

extent of “intactness” of the skin influences penetration

  • defective/partially removed stratum corneum - increased percutaneous absorption (cuts, abrasions, burns)
  • tape stripping the skin removes the stratum corneum and increases drug penetration dramatically (40-50x for steroids)
  • defective epidermis due to disease increases percutaneous absorption
  • diseases causing thickening of stratum corneum usually decrease percutaneous absorptio
39
Q

Biological Factors Affecting Percutaneous Absorption

Skin Age

A
  • children and elderly generally have more permeable skin
  • children have a greater surface area to weight ratio than adults (ie. neonates = 4x adults)
  • enhanced penetration can result in side effects after long-term topical steroid administration – growth impairment in children, skin atrophy in older skin (thin, pliable skin with visible underlying blood vessels)
40
Q

Biological Factors Affecting Percutaneous Absorption

Regional Skin Sites

A
  • thickness, hydration of the stratum corneum and density of appendages influences percutaneous absorption
  • high permeability sites: post auricular, face, chest, forehead, scrotum
  • low permeability sites: hands, feet, lower
    arms, leg
41
Q

Biological Factors Affecting Percutaneous Absorption

Skin Hydration and Occlusion

A
  • when water saturates the skin (i.e., the stratum corneum), it swells, softens any wrinkles, and percutaneous absorption is markedly increased
  • the compact structure of the stratum corneum is opened up, producing a decreased density of keratin fibres and increased free volume
  • natural moisturizing factor (NMF) components can hydrate the skin (fatty acids, urea, lactic acid, pyrrolidone carboxylic acid) and increase percutaneous absorption
42
Q

Biological Factors Affecting Percutaneous Absorption

What is occlusion?

A

the use of impermeable films (plastic) or lipid/oily films on the surface of skin to trap moisture and reduce water loss

  • this hydrates the stratum corneum and increases percutaneous absorption
43
Q

Physicochemical Factors Affecting Percutaneous Absorption

Partition Coefficient

A
  • Ksv is very important factor but very hard to measure
  • K0w correlates well with Ksv and is easily measure
  • optimal K0w for most topical steroids is in the range of 1000-10,000
  • steroids are usually converted to more hydrophobic esters – increase their hydrophobicity, increase K0w and percutneous absorption
44
Q

Physicochemical Factors Affecting Percutaneous Absorption

What happens if the partition coefficient (K0w) is increased beyond an optimal value?

A

percutaneous absorption will decrease

  • drug is too hydrophobic to partition into the viable epidermis layer (containing more water)
45
Q

Physicochemical Factors Affecting Percutaneous Absorption

Drug Concentration and Solubility

A
  • low solubility of drug in vehicle causes a situation where drug dissolution is limited and hence drug diffusion through vehicle becomes rate controlling – drug must dissolve in vehicle
  • increase in the concentration of drug in solution in the vehicle (Cv) increases percutaneous absorption
  • co-solvents such as propylene glycol, glycerol, alcohol increase drug solubility in an aqueous vehicle and can be used to increase Cv – excessive co-solvents will decrease the Ksv (by keeping the drug in the vehicle) therefore only minimum amount of co-solvent is used to just dissolve the drug (ideally, vehicles should be close to saturation with respect to the drug)
46
Q

Physicochemical Factors Affecting Percutaneous Absorption

What do co-solvents do?

A
  • decrease the polarity of aqueous sites in the intercellular lipid region
  • increase the effective solubility of a drug in the stratum corneum
  • increase Ksv and therefore increasing flux
  • this alters the intercellular route
47
Q

Physicochemical Factors Affecting Percutaneous Absorption

What do penetration enhancers do?

A

reduce the barrier effect of the skin and allow the drug to reach viable tissues of the skin at faster rates without tissue damage

  • ie. surfactants, co-solvents, pyrrolidones
48
Q

Physicochemical Factors Affecting Percutaneous Absorption

How do penetration enhancers act?

A

alter intercellular lipid:

  • insert between polar head groups in lipid bilayers, modifying H-bonding, ionic forces, hydration shells and upsetting lipid packing
  • insert between the acyl chains of the lipid bilayers, increasing disorder and fluidity and allowing for more rapid flux of drugs
  • this alters the intercellular route

alter intracellular keratin:

  • cause conformational changes in keratin molecules leading to opening of channels or pores which enhance drug penetration
  • this alters the transcellular route

PHRM 100 – PDD (14 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions