Semisolids Flashcards
Identify the layers of the skin and their main functions. Which layer represents the main
skin barrier?
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
What is the skin surface pH? Define acid mantle.
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
What is the average thickness of the layers of skin
Epidermis: 200 microm (800microm thick skin, 60 microm eyelid)
Stratum corneum: 10-20 microm
Dermis: 1-5 mm
What is percutaneous absorption influenced by?
- 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
What is water content of the normal stratum corneum
10-20%
What does the shunt route of drug permeation mean?
Shunt route = absorption through the appendages
What effect does UV light have on the skin?
UVB 290 - 320 nm ⇒ burns skin
UVA 320 - 400 nm ⇒ less damaging (aging, pigmentation
skin response to UV radiation (Pigmentation, erythema, aging, malignancy)
The skin is an important heat barrier:
What is the consequence of heat or cold exposure on the skin vasculature and percutaneous absorption?
Heat conservation (vasoconstriction, shivering, goose bumps, cold)
- percutaneous absorption decreases
- Heat loss (vasodilation, skin reddening)
percutaneous absorption increases
Define “sink conditions”
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
Define ointments, creams, pastes, gel
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
Which bases are non water washable bases and water washable vehicles?
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
Define occlusion and effects on the skin
- 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)
What are properties of oleaginous/hydrocarbon bases?
Provide examples
- 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
What are properties of Absorption bases and give examples
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
Differentiate between wool fat (anyhdrous lanolin) and lanolin
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
Define cold cream and the traditional emulsifier used for it
W/O emulsion bases
- contain beeswax-borax type in situ emulsifier)
- cetyl esters wax
- White wax
What are properties of w/o emulsions non-water washable bases
Properties
- more greasy
- Emollient (cleansing cream)
- Capable of absorbing oil-soluble compounds from the skin (makeup removers)
What are properties of non-water washable pastes?
Properties
- ointments containing up to 50% powder dispersed in fatty bases
- Very stiff consistency
- Form a thick impermeable layer on the skin
What are properties for silicon bases non-water washable bases
- Used as skin barrier to protect skin
- concentration in ointments 10-30%
What are the properties of water washable bases
- waterwashable
- Soft
- Non-occlusive
- Moisturizing
- Penetration enhancement of the drug compounds
Define vanishing cream and the traditional emulsifier used for it
- o/w emulsion base
- Stearic acid and KOH form potassium stearate in situ
- Smooth, easy to apply
- No residue
What does a cleansing o/w cream look like have?
- stearic acid 25g
- mineral oil 57 g
- lanolin 34 g
- Triethanolamine 10g
- propylene glycol 24 g
- Water 150g
What are some gel-forming materials
- Natural gums
- Methylcellulose, hydroxymethcylcellulose etc.
- Carbopol
- Bentonite
What are properties of hydrophilic bases and examples
- 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)
What are example of emulsifying bases?
Sodium laurylsulfate (anionic)
Cetrimide (cationic)
Cetomacrogol (Non-ionic)
What is the reason for using the following additives to dermatological vehicles? Give
example for each group.
Humectants
Levigating agents
Penetration enhancers
Antioxidants
Preservative
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
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
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
. What type of dermatological base can be used:
On oozing and weeping dermatoses?
On dry scaly skin?
On hairy skin?
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
Describe the process of permeation of molecules?
- 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
What layers are topical delivery vs. transdermal delivery?
Topical: epidermis, dermis
transdermal: circulation (hypodermis)
What is the ‘brick-and-mortar’ model and how is it used to explain drug permeation?
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
Indicate how the following factors influence percutaneous absorption (PA):
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
What determines potency?
What is the order of potency for external application products?
Drug class not drug %
ointment>cream>lotion>gel>foam/spray/solution
Can tolerance occur on topical corticosteroids
Yes
What is FTU and how is it used for dosing topical preparations
FTU = fingertip unit
1 FTU=0.5g cream = treats 2% body surface area
Rule of hand= 4 hand areas=2 FTU = 1g cream
Define rheology and viscosity
Rheology
- study of changes in form, shape and flow
Viscosity
- resistance to flow
Describe Newtonian and non-Newtonian flow behaviour
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
What are the types of non-newtonian systems and affect on shear stress and viscosity it has. (3)
And examples
- Plastic flow (bingham flow)
- need a critical value of shear stress (yield value)
- will have shear thinning (viscosity decrease)
Ex. flocculated sus, ointments, cream - Pseudoplastic flow
- No yield value for shear stress (will plateu)
- Shear thinning: decrease viscosity while increase shear rate
Ex. polymers, gelatin, methylcellulose - Dilatant flow
- Exponential shear stress
- Shear thickening for viscosity
Ex. deflocculated sus.
Define thixotropy
- Reversible
- Time-dependent decrease in apparent viscosity
