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PHARM 124 Final > Semisolids > Flashcards

Semisolids Flashcards

1
Q

Identify the layers of the skin and their main functions. Which layer represents the main
skin barrier?

A

Epidermis

Stratum corneum (horny layer)
– the main barrier **controls percutaneous
absorption (dead corneocytes)
Stratum lucidum (clear layer) transitionary layer
Stratum granulosum (granular layer)
- Keratinocytes contain keratohyalin granules
which discharge a cement-like substance that bind cells together (barrier against
foreign material); Site of biochemical activity (bioreactor)
Stratum spinosum (prickle cell layer)
- Keratinocytes contain bundles of filaments
(“prickly” looking) which help skin to resist abrasion
Stratum germinativum/basale (basal layer)
- Nucleated basal cells , dividing
(mitosis) layer which replaces the shedding cells of stratum corneum)

Dermis
– sensation, blood circulation, immune function
- Site for drug metabolism
- Hair follicles, sebaceous glands, sweat glands (appendages)

Subcutaneous tissue – support, mechanical cushioning, thermal barrier, subcutaneous tissue

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2
Q

What is the skin surface pH? Define acid mantle.

A

5.5

Acid mantle pH 4.2 - 5.6 → bacteriostatic and fungistatic secretions (short chain fatty acids from
sebaceous and eccrine sweat glands) – formulations with pH 5.5 are said to be the most compatible with the skin

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3
Q

What is the average thickness of the layers of skin

A

Epidermis: 200 microm (800microm thick skin, 60 microm eyelid)
Stratum corneum: 10-20 microm

Dermis: 1-5 mm

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4
Q

What is percutaneous absorption influenced by?

A
  • Blood vessels: maintain sink conditions; vasoconstriction and vasodilation due to cold
    and heat decreases or increases drug absorption, respectively
  • Appendages: pores of appendages can allow drug absorption, however, this ‘shunt route’
    provides for very low absorption due to the small fraction of area (0.1% of total area)
    occupied by hair follicles and glands
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5
Q

What is water content of the normal stratum corneum

A

10-20%

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6
Q

What does the shunt route of drug permeation mean?

A

Shunt route = absorption through the appendages

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7
Q

What effect does UV light have on the skin?

A

UVB 290 - 320 nm ⇒ burns skin
UVA 320 - 400 nm ⇒ less damaging (aging, pigmentation
skin response to UV radiation (Pigmentation, erythema, aging, malignancy)

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8
Q

The skin is an important heat barrier:
What is the consequence of heat or cold exposure on the skin vasculature and percutaneous absorption?

A

Heat conservation (vasoconstriction, shivering, goose bumps, cold)
- percutaneous absorption decreases

  • Heat loss (vasodilation, skin reddening)
    percutaneous absorption increases
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9
Q

Define “sink conditions”

A

Blood circulation in the DERMIS maintains sink conditions by taking up drug absorbed into skin
into the systemic circulation thereby maintaining high concentration gradient between the
formulation and the skin

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10
Q

Define ointments, creams, pastes, gel

A

Ointment
- hydrophobic or greasy
- Anhydrous
- Single phase vehicles

Cream
- Contain both oil phase and water

Paste
- 20-50% of solids finely dispersed in a fatty vehicle

Gel
- provide stiffness to a solution or colloidal dispersion
- good for hairy areas
- water-soluble drugs

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11
Q

Which bases are non water washable bases and water washable vehicles?

A

non water washable bases
- Oleaginous/hydrocarbon bases
- Absorption bases
- W/O emulsion bases
- Silicone bases

Water washable vehicles
- O/W emulsions
- Gels
- Hydrophilic bases
- Emulsifying bases

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12
Q

Define occlusion and effects on the skin

A
  • formation of an impermeable layer on the skin to prevent evaporation of water

Effects:
- Increased hydration (by preventing evaporation of water from the skin)
- Enhanced percutaneous absorption
- Softening of the skin (emollient action)

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13
Q

What are properties of oleaginous/hydrocarbon bases?

Provide examples

A
  • Hydrophobic
  • Greasy
  • Non-water washable
  • Occlusive
  • Emollient

Excipients
- fixed oils (peanut, cottonseed, almond)
- Waxes (esters of fatty acids)

Vehicles
- Petrolatum
- Yellow, white, zinc oxide ointment

Plastibase
- polyethylene
- Mineral oil

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14
Q

What are properties of Absorption bases and give examples

A

Properties
- Hydrophobic
- Greasy
- Anhydrous (hydrophilic components provide water-absorbing properties)
- W/O after adding water

Examples
- Anhydrous lanolin (wool fat)
- Lanolin (hydrous wool fat)
- Lanolin alcohols, liquid lanolin
- Hydrophilic petrolatum
- Aquabase ointment
- Wool alcohols ointment

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15
Q

Differentiate between wool fat (anyhdrous lanolin) and lanolin

A

wool fat (anyhdrous lanolin)
- contains mixture of sterols which impact the ability to absorb water
- water content: LESS THAN 0.25%

Lanolin
- 25-30% water

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16
Q

Define cold cream and the traditional emulsifier used for it

A

W/O emulsion bases
- contain beeswax-borax type in situ emulsifier)
- cetyl esters wax
- White wax

17
Q

What are properties of w/o emulsions non-water washable bases

A

Properties
- more greasy
- Emollient (cleansing cream)
- Capable of absorbing oil-soluble compounds from the skin (makeup removers)

18
Q

What are properties of non-water washable pastes?

A

Properties
- ointments containing up to 50% powder dispersed in fatty bases
- Very stiff consistency
- Form a thick impermeable layer on the skin

19
Q

What are properties for silicon bases non-water washable bases

A
  • Used as skin barrier to protect skin
  • concentration in ointments 10-30%
20
Q

What are the properties of water washable bases

A
  • waterwashable
  • Soft
  • Non-occlusive
  • Moisturizing
  • Penetration enhancement of the drug compounds
21
Q

Define vanishing cream and the traditional emulsifier used for it

A
  • o/w emulsion base
  • Stearic acid and KOH form potassium stearate in situ
  • Smooth, easy to apply
  • No residue
22
Q

What does a cleansing o/w cream look like have?

A
  • stearic acid 25g
  • mineral oil 57 g
  • lanolin 34 g
  • Triethanolamine 10g
  • propylene glycol 24 g
  • Water 150g
23
Q

What are some gel-forming materials

A
  • Natural gums
  • Methylcellulose, hydroxymethcylcellulose etc.
  • Carbopol
  • Bentonite
24
Q

What are properties of hydrophilic bases and examples

A
  • Anhydrous (cannot take up more than 8% water)
  • non-occlusive
  • greaseless
  • Water washable, non-irritant
  • Chemically stable: do not hydrolyze

Examples:
PEG 3350 (solid)
PEG 300 (liquid)

25
Q

What are example of emulsifying bases?

A

Sodium laurylsulfate (anionic)
Cetrimide (cationic)
Cetomacrogol (Non-ionic)

26
Q

What is the reason for using the following additives to dermatological vehicles? Give
example for each group.

Humectants
Levigating agents
Penetration enhancers
Antioxidants
Preservative

A

Humectants
- increase skin hydration
Eg. glycerol, PEG, propylene glycol

Levigating agents
- aid particle size reduction
Eg. mineral oil, caster oil, glycerol

Penetration enhancers
- Temporarily increase permeability of the skin to allow drug to pass
eg. chemical penetration enhancers, specialized delivery system

Antioxidants
- prevent rancidity due to oxidation
eg. BHA, BHT, ascorbic acid, sulfites, Vitamin E

Preservative
- protect from microbial growth
eg. alcohol, benzoic acids, quratnery ammonium compounds

27
Q

Indicate the type of dermatological vehicle preferred in the following dermatological
conditions and why:

Acne
Alopecia
Dermatitis/Eczema
Psoriasis
Urticaria
Herpes
Corns and calluses
Athletes foot

A

Acne
- liquids, gels, creams o/w emulsion
- base should NOT be occlusive (since acne is plugged pores and oily skin surface)

Alopecia
- water or alcohol liquids, gels, creams
- Should be easy to apply on hairy areas and non-greasy (gels)

Dermatitis/Eczema
- creams, lotions
- Base should NOT be occlusive (oozing condition)

Psoriasis
- Occlusive (hydrocarbons, silicon bases, creams, ointments with plastic wrap)
- bases should BE occlusive and increase hydration

Urticaria
- gels, shake lotions, creams
- NOT occlusive (should help cool and soothe burning and itching)

Herpes
- lotions, PEG base, gels
- NOT occlusive

Corns and calluses
- OCCLUSIVE ointment bases
- should provide softening and moisturization

Athletes foot
- o/w creams, powders
- NOT OCCLUSIVE

28
Q

. What type of dermatological base can be used:
On oozing and weeping dermatoses?
On dry scaly skin?
On hairy skin?

A

On oozing and weeping dermatoses? Liquids, pastes, o/w creams

On dry scaly skin? Ointments (all types), o/w and w/o creams, pastes, liquids

On hairy skin? Gels, liquids, o/w creams

29
Q

Describe the process of permeation of molecules?

A
  • Governed by Fick’s law
  • the rate limiting factor for drug diffusion is the stratum corneum
  • highly hydrophobic drug molecules can form a depot in the SC or dermis eg. corticosteroids
30
Q

What layers are topical delivery vs. transdermal delivery?

A

Topical: epidermis, dermis
transdermal: circulation (hypodermis)

31
Q

What is the ‘brick-and-mortar’ model and how is it used to explain drug permeation?

A

The structure of the stratum corneum is described as brick-and-mortar where the
- bricks = corneocytes (protein/cells)
- mortar = lipid (between the cells)

The two pathways for drug
absorption are : intercellular – through the lipid channels BETWEEN the cells and
intra/transcellular – THROUGH the cells

32
Q

Indicate how the following factors influence percutaneous absorption (PA):

A

a. Concentration of drug in the vehicle
↑ drug conc in vehicle = ↑ PA

b. Drug metabolism in the skin
=↓ PA

c. Vehicle-to-stratum corneum partition coefficient
=↑ PA

d. Ionization state of the drug
non-ionized drug = ↑ PA better

e. Supersaturation of drug in the vehicle by co-solvents. (hydrophilic solvents)
- ↑ PA

f. Presence of penetration enhancers in the vehicle
- ↑ PA

g. Vasodilation in dermis= ↑ PA
vasoconstriction = ↓ PA

h. Dry skin = ↓ PA
fully hydrated skin = ↑ PA

i. Age of the skin
infant = more permeable
adult skin = less permeable

j. Different regions of the skin
- permeability varies as thickness of stratum corneum varies
(thin SC on eyelids, behind the ear)

k. Animal versus human skin
- animal skin is more permeable compared to human skin

33
Q

What determines potency?
What is the order of potency for external application products?

A

Drug class not drug %

ointment>cream>lotion>gel>foam/spray/solution

34
Q

Can tolerance occur on topical corticosteroids

A

Yes

35
Q

What is FTU and how is it used for dosing topical preparations

A

FTU = fingertip unit
1 FTU=0.5g cream = treats 2% body surface area
Rule of hand= 4 hand areas=2 FTU = 1g cream

36
Q

Define rheology and viscosity

A

Rheology
- study of changes in form, shape and flow

Viscosity
- resistance to flow

37
Q

Describe Newtonian and non-Newtonian flow behaviour

A

Newtonian flow: flow in which viscosity is a constant value viscosity doesn’t change with the force applied to it
- one point determination (graph)
- Ex. water, alcohol, glycerol

Non-Newtonian flow: Flow in which viscosity is NOT a constant value → viscosity changes with
the force applied to it
- viscosity changes with shear rate
- Determination at more than 1 shear rate
- Ex. plastic flow, pseudoplastic flow, dilatant flow

38
Q

What are the types of non-newtonian systems and affect on shear stress and viscosity it has. (3)
And examples

A
  1. Plastic flow (bingham flow)
    - need a critical value of shear stress (yield value)
    - will have shear thinning (viscosity decrease)
    Ex. flocculated sus, ointments, cream
  2. Pseudoplastic flow
    - No yield value for shear stress (will plateu)
    - Shear thinning: decrease viscosity while increase shear rate
    Ex. polymers, gelatin, methylcellulose
  3. Dilatant flow
    - Exponential shear stress
    - Shear thickening for viscosity
    Ex. deflocculated sus.
39
Q

Define thixotropy

A
  • Reversible
  • Time-dependent decrease in apparent viscosity

PHARM 124 Final (3 decks)

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