Semi-solids Flashcards
what is the largest organ in the body
the skin
what does every cm^2 of the skin contain
10 hair follicles 12 nerves 15 sebaceous glands 100 sweat glands 3 blood vessels 3 million cells
what is the pH of the skin
5.5 (acid mantle)
what is the thickness of the epidermis
average: 200 μm
palms and soles: 800 μm
eyelid: 60 μm
what is the thickness of the dermis
1-5 mm
what are the layers of the epiderms
stratum corneum stratum lucidum stratum granulosum stratum spinosum stratum basale
Which layer of the skin is the site for drug metabolism
dermis
what products target the skin surface
cosmetics
protective films (sunscreens)
antifungal/antibacterial (ex. polysporin)
what products target the stratum corneum
emollients and moisturizers (increase water content)
keratolytics (remove dead cells)
what products target skin appendages
antiperspirants (aluminum salts) exfoliants (salicylic acid, tretinoin) depilatories antibiotics antifungals
what products target the epidermis/dermis
anti-inflammatory agents
local anesthetics
antihistamines
anticancer drugs
what products target percutaneous absorption (systemic treatment)
motion sickness (scopolamine)
angina (nitroglycerin)
hypertension (clonidine)
smoking cessation (nicotine)
What are the types of dermatological vehicles
ointments creams/lotions pastes gels aerosols powders liquids
what are the 2 types of vehicles based on STRUCTURE
ointments (single phase)
creams (two phase - either o/w or w/o)
these categories are not based on viscosity
What are the types of vehicles based on WASHABILITY
non-water washable
water washable
what is an ointment
A suspension or emulsion of semisolid dosage form that contains <20% water and volatiles and >50% of hydrocarbons, waxes, or polyethylene glycols as the vehicle for external application to the skin
what is a cream
An emulsion semisolid dosage form that contains >20% water and volatiles and <50% of hydrocarbons, waxes, or polyethylene glycols as the vehicle for external application to the skin
what is a paste
A semisolid dosage form that contains a large proportion (i.e. 20-50%) of solids finely
dispersed in a fatty vehicle for external application to the skin
what is a lotion
An emulsion liquid dosage form for external application to the skin
what is a gel
A semisolid dosage form that contains a gelling agent to provide stiffness to a solution or colloidal dispersion for external application to the skin. A gel may contain suspended particles
what is a topical suspension
A liquid dosage form that consists of a solid suspended in a liquid vehicle in a two- phase system for external application on the skin
what is a topical solution
A clear homogeneous liquid dosage form for external application to the skin
what are the types of non-water washable bases
Oleaginous/Hydrocarbon bases
Absorption bases
Water in oil (W/O) emulsion bases
Silicone bases
what is an occlusion
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
- Hydrophobic
- Greasy
- Non-water washable
- Occlusive
- Emollient
what are advantages of Oleaginous/Hydrocarbon bases
Very stable vehicles
Non-irritating
Non-sensitizing
High compatibility with drugs
what are disadvantages of Oleaginous/Hydrocarbon bases
Greasiness
Stain clothing
Difficult to remove
Low patient acceptance
examples of excipients in Oleaginous/Hydrocarbon bases
- fats and fixed oils - susceptible to oxidation, become rancid (ex. vegetable oils)
- waxes - stiffening agents (increase viscosity) - (ex. white wax, hard paraffin)
Vehicles in Oleaginous/Hydrocarbon bases
- petrolatum, white petrolatum (greasy, high mp)
2. plastibase/oleo-gel (greasy, stains, lower mp, drugs released faster than petrolatum)
What are properties of absorption bases
Hydrophobic
Greasy
Anhydrous; hydrophilic components provide water- absorbing properties
Upon water addition form W/O emulsions
Examples of absorption bases
- anhydrous lanolin/wool fat (takes up 2x its weight in water)
- lanolin/hydrous wool fat (takes up limited amounts of water)
Properties of W/O emulsions
More greasy than O/W emulsions
Emollient, cleansing action
Capable of absorbing oil-soluble compounds from the skin e.g. make-up removers
Examples of W/O emulsions
- Cold creams (beeswax-borax system- in situ emulsifier)
2. Emollient creams (Rose water ointment, USP)
Properties of pastes
Ointments containing up to 50% powder dispersed in fatty base
Very stiff consistency – localize materials to defined areas of the skin
Form a thick impermeable layer on the skin – protective action
Properties of silicon bases
Fluid polymers with properties similar to hydrocarbon bases Hydrophobic Used as barrier to protect the skin (diaper rash, bed sores) Concentration in ointments 10-30%
What are the types of water washable bases
O/W emulsions
Gels
Hydrophilic bases
Emulsifying base
Properties of O/W emulsions
Water washable
Soft
Non-occlusive
Moisturizing (increases water content -> restores hydration of the skin)
Penetration enhancement of the drug compounds
What is vanishing cream
- Stearic acid and KOH form potassium stearate in situ
- Smooth, easy to apply
- Instantaneous absorption to the skin
- No residue
What are gels
two-component (liquid and polymer) colloidal system
what are gel-forming materials
- Natural gums: tragacanth, agar, pectin, alginates
- Semi-synthetic or synthetic polymers: methylcellulose, hydroxymethylcellulose, hydroxypropylcellulose,
- Synthetic polymers: carbopol
- Clays: bentonite
Properties of gels
- Dissolve in water
- Good for hairy areas
Properties of hydrophilic bases
- Anhydrous -> useful for drugs that hydrolyze
- Good patient compliance – non-staining, non-occlusive
- Ointment-like consistency (soften or melt on the skin)
- Water-washable
- Non-irritant
- Chemically stable: do not hydrolyze, deteriorate, do not support mold growth
- Cannot take up more than 8% water (loose consistency)
Properties of emulsifying bases (ointment)
Anhydrous bases containing O/W emulsifying agents
Miscible with water
Self-emulsifying (does not need excipients)
Cream-like appearance
Water- washable
What is a levigating agent
• A levigating agent is a liquid used as an intervening agent to aid the incorporation
and particle size reduction of a powder into an ointment
• Maximum 5% of final formulation
e.g: mineral oil, glycerol
What is a penetration enhancer
• Temporarily increase the permeability of the skin to allow drug molecules to pass
eg,. chemical permeation enhancers, specialized delivery systems
What are properties of an ideal penetration enhancer
- Pharmacologically inert
- Non-toxic, non-irritating, non-allergenic
- Immediate and predictable effect
- Immediate recovery of the barrier property of the skin after removal of the agent
- Should not cause loss of body fluids, electrolytes or other endogenous materials
- Compatible with drugs and excipients
- Good drug solvent
- Cosmetically acceptable (good spreadability and “feel”)
- Readily formulated into the various types of topical preparations
- Odourless, tasteless, colourless and inexpensive
What are examples of permeation enhancers
Fatty acids (Oleic acid)
Alcohols, glycols (ethanol, propylene glycol)
Surfactants (SDS, Tween 80)
Urea
Examples of antimicrobial preservatives
Alcohols: ethanol, isopropanol Acids: benzoic acid Mercurials: thimerosal Phenols: phenol, cresol p-hydroxybenzoates: methyl-, propyl-, butylparaben Quaternary ammonium compounds: benzalkonium chloride, cetrimide
How to determine which formulation to be used on skin
Chart on page 49
What is the pathophysiology of acne
- inflammation of sebaceous gland = increase in sebum production
- Free fatty acids produced by P. acnes bacteria
- desquamating stratum corneum cells and sebum form “plug” in the sebaceous follicles
What is the therapy for acne
- Bacteriostatics: benzoyl peroxide
- Topical antibiotics
- Exfoliants: sulfur, resorcinol, tretinoin, salicylic acid, benzoyl peroxide
What bases are used for acne
- liquids (water or alcohol based)
- gels
- creams, o/w emulsions
- Do NOT use occlusive bases
Pathophysiology of alopecia
Natural or abnormal loss of hair on the scalp
- family history, androgenic influences, aging, systemic disorders
What are the types of alopecia
Alopecia totalis → no hair
Alopecia areata → patchy hair loss
Treatment of alopecia
No satisfactory treatment (possibly Minoxidil/Rogaine)
Types of bases used for alopecia
- water or alcohol based liquids
- gels
- creams
Pathophysiology of dermatitis (eczema)
Superficial inflammation of the skin.
Types:
- atopic dermatitis (allergic condition)
- contact dermatitis (delayed hypersensitivity reaction)
What is the treatment used for dermatitis
Emollients
Astringents
Antipruritics
Topical corticosteroids
Types of bases used for dermatitis
creams
lotions
try to avoid occlusion
What is psoriasis and how does it look
Chronic inflammatory skin disease.
- red patches on the scalp or extremities — may be generalized
- lesions that are covered with silvery-white scales that produce bleeding if removed
Treatment of psoriasis
Emollients (hydration)
Keratolytics (remove scales)
Corticosteroids (treat inflammation)
Types of bases used for psoriasis
occlusive (the more the better) → hydrocarbons, silicon bases
creams
ointments with plastic wrap (↑ hydration)
What is Urticaria and what does it look like
A vascular reaction to insect bites, diet or drugs.
- wheals surrounded by a halo accompanied
by severe itching and burning
What is the treatment for urticaria
Topical astringents
Anti-inflammatory lotions
Anti-histamines
Types of bases used for urticaria
non-occlusive
gels
shake lotions (cool — relieve burning and itching)
creams
What is Herpes Simplex and what does it look like
Recurrent viral infection of the skin and mucous membranes.
- vesicles appearing in clusters on erythematous base — associated with tingling and itching
Treatment of Herpes Simplex
Topical antiviral preparations
Lotions containing camphor and tannic acid
Types of bases used for herpes simplex
non-occlusive
liquid lotions
PEG
gels
What are corns and calluses and what do they look like
Corns ⇒ raised conical hyperkeratinous lesions extending down to the dermis and pressing inward on the nerve endings causing pain and irritation.
Calluses ⇒ circumscribed thickenings of the skin due to friction, pressure.
- usually dry thickenings of the skin on or between toes, etc.
Therapy for corns and calluses
Remove causative factor
Keratolytics (salicylic acid > 10%, resorcinol)
Caustics (lactic acid, trichloroacetic acid emulsions)
Emollients
Types of bases used for corns and calluses
occlusive - the more the better (easier to remove by abrasion)
collodions (liquid with organic solvents + polymer that deposits on skin)
What is athlete’s foot and what does it look like
Superficial fungal infection of the skin.
- small blisters between toes (blisters may break and become hard and scaly), cracks, redness, maceration, itching, burning
Therapy for athlete’s foot
Thoroughly dry feet after shower/bath.
Antifungal powders
Topical antifungal creams
What types of bases are used for athlete’s foot
non-occlusive
o/w creams
What are topical corticosteroids?
- contain derivatives of the natural corticosteroid hormones that are produced by the adrenal glands
- are mainly applied to the skin for the localised treatment of various inflammatory skin conditions
What is the parent molecule of most corticosteroids
Hydrocortisone (it’s not very potent so modifying structure increases its potency)
How does concentration affect absorption of topical corticosteroids
Higher concentrations will increase the potency
How does hydration affect absorption of topical corticosteroids
Application to hydrated skin after bathing can increase absorption 4-5 fold
What factors influence topical corticosteroids absorption kinetics
- concentration
- hydration
- occlusion
- penetration enhancers (propylene glycol, urea, salicylic acid)
- mixing of bases (can increase or reduce potency)
How are topical corticosteriods classified
classified according to their relative potencies. (Class I = ultra high potency and Class VII = lowest potency)
Super/Ultra high potency (Class I) topical corticosteroids
- greater inflammatory effect (therefore higher risk of side effects)
- used on non-facial, thick skin, or where penetration is poor (elbows, knees)
- should not be used with occlusive dressing
Medium to high potency (Classes II-V) topical corticosteroids
- Used for mild to moderate nonfacial and nonintertriginous areas
Lower potency (Class VI and VII) topical corticosteroids
- preferred on areas where penetration is high and on thin skin areas (face, eyelid, axilla, genital and intertriginous areas)
- recommended in young children, infants and elderly (more prone to local and systemic side effects)
- recommended in case of long term therapy or application to large areas
Can the same topical corticosteriod be in different classes
Yes, the vehicles used can change the potency ex. Betamethsone valerate 0.1% is class III as an ointment, class V as a cream, and class VI as a lotion
What is the order of potency for different formulations
ointment>cream>lotion>gel>foam/spray/ solution
What is the order of potency for different formulations
ointment>cream>lotion>gel>foam/spray/ solution
When should ointments be chosen as the vehicle for topical corticosteriods
- preferred in treating chronic lesions (psoriasis) or young children with infantile atopic dermatitis where dryness of the skin is a particular problem
- should not be used in areas such as the axilla, groin, or skin folds due to their occlusive effect and high risk of corticosteroid side effects
When should creams be chosen as the vehicle for topical corticosteriods
- preferred for non-acute dermatoses as they are cosmetically more acceptable
- proper application requires rubbing fully into the skin in such a way that a residue is not visible after application
When should lotions be chosen as the vehicle for topical corticosteriods
- non-occlusive, easy to apply
- useful when large skin areas or skin flexures are affected
- Some lotions, such as scalp lotions, are suitable for hairy areas
When should gels be chosen as the vehicle for topical corticosteriods
- non-greasy, non-occlusive, non-staining, and quick drying
* most useful when applied to hairy or facial areas where residue from a vehicle is unacceptable
When should foams, sprays or solutions be chosen as the vehicle for topical corticosteriods
- non-greasy, non-occlusive, non-staining, and quick drying; if contains alcohol it can be very drying and can sting sore skin
- used on scalp and hairy areas
what are local side effects of topical corticosteroids
Skin atrophy: Usually occurs after several weeks of
treatment (reversible)
Striae: Most common around the groin, axillae, and inner thigh (Usually not reversible)
Telangiectasia: Visible distended capillaries. Often seen on the face, neck, chest (Usually reversible)
Purpura: Bruising with minimal trauma
Fine hair growth, hypertrichosis
Acne like eruptions: Common on the face, reversible
Hypopigmentation: Especially in dark skinned people Rebound dermatitis: occur with sudden discontinuation
Mask fungal infections
What are systemic side effects of topical corticosteroids
- Hypothalamic-pituitary axis suppression - Cushing’s syndrome - hyperglycemia - growth retardation in children - Glaucoma (when applied to eyelid) - Hypertension
How to limit side effects of topical corticosteroids
- The higher the potency the higher the risk for side effects
- To reduce the risk, the least potent steroid should be used for the shortest time
How to prevent tolerance (tachyphylaxis) of topical corticosteroids
can be prevented by limiting the long term application to once or twice daily or by stopping the therapy for a few days
How often should topical corticosteroids be applied
- can be applied OD to QID, but OD-BID is preferred to reduce risk of side effects
What does “apply sparingly” mean
Clarify that “It is important to apply just enough to cover the affected area”
What is the fingertip unit (FTU)
1 FTU = 1/2 g (500mg) = treats 2% BSA
1 palm = 1% BSA (patients palm)
What is the rule of hand
4 hand areas = 2 FTU = 1 g cream
What is the rate limiting factor for diffusion across the skin
the stratum corneum
How does Fick’s Law apply to drug permeation across the skin
concentration gradient determines diffusion properties
Where do highly hydrophobic drugs from a depot
in the stratum corneum or in the dermis (ex. corticosteroids)
What is the target delivery site of topical formulations vs. transdermal therapeutic systems
topical: target = skin
patch: target = systemic system
what are the routes for percutaneous absorption
- across the stratum corneum - brick and mortar model (bricks = protein/cells, mortar = lipid)
- via appendages (Sweat ducts, Sebaceous glands, Hair follicles)
What are the drug factors influencing percutaneous absorption
- Higher concentration of the drug = faster absorption (↑ concentration gradient)
- partition coefficient (P) - hydrophic drugs will absorb easier
- Vehicle-to-stratum corneum partition
- ratio of conc. drug in stratum corneum to the conc. drug in the vehicle
- Kp (permeability coefficient) large: ↑ partitioning
- drug/skin binding (↑ residence time, therefore decreases percutaneous absorption)
What are the vehicle factors influencing percutaneous absorption
- pH → Determines ionization of the drug (unionized = more hydrophobic = permeates better into skin)
- co-solvents → concentrate drug on skin (↑ c gradient)
- release of drug from vehicle → optimize with the appropriate vehicle
- penetration enhancers temporarily ↑ permeability of the skin
What are the skin factors influencing percutaneous absorption
- age of the skin (children vs. adults (adults are less permeable))
- skin condition (e.g., hydration of stratum corneum, disease state)
- thickness of stratum corneum (thinner skin = more permeable)
- skin metabolism
- circulation effects (vasoconstriction decreases permeability)
- species differences (animals vs. humans)
