Semi-solids Flashcards
(107 cards)
1
Q
what is the largest organ in the body
A
the skin
2
Q
what does every cm^2 of the skin contain
A
10 hair follicles 12 nerves 15 sebaceous glands 100 sweat glands 3 blood vessels 3 million cells
3
Q
what is the pH of the skin
A
5.5 (acid mantle)
4
Q
what is the thickness of the epidermis
A
average: 200 μm
palms and soles: 800 μm
eyelid: 60 μm
5
Q
what is the thickness of the dermis
A
1-5 mm
6
Q
what are the layers of the epiderms
A
stratum corneum stratum lucidum stratum granulosum stratum spinosum stratum basale
7
Q
Which layer of the skin is the site for drug metabolism
A
dermis
8
Q
what products target the skin surface
A
cosmetics
protective films (sunscreens)
antifungal/antibacterial (ex. polysporin)
9
Q
what products target the stratum corneum
A
emollients and moisturizers (increase water content)
keratolytics (remove dead cells)
10
Q
what products target skin appendages
A
antiperspirants (aluminum salts) exfoliants (salicylic acid, tretinoin) depilatories antibiotics antifungals
11
Q
what products target the epidermis/dermis
A
anti-inflammatory agents
local anesthetics
antihistamines
anticancer drugs
12
Q
what products target percutaneous absorption (systemic treatment)
A
motion sickness (scopolamine)
angina (nitroglycerin)
hypertension (clonidine)
smoking cessation (nicotine)
13
Q
What are the types of dermatological vehicles
A
ointments creams/lotions pastes gels aerosols powders liquids
14
Q
what are the 2 types of vehicles based on STRUCTURE
A
ointments (single phase)
creams (two phase - either o/w or w/o)
these categories are not based on viscosity
15
Q
What are the types of vehicles based on WASHABILITY
A
non-water washable
water washable
16
Q
what is an ointment
A
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
17
Q
what is a cream
A
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
18
Q
what is a paste
A
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
19
Q
what is a lotion
A
An emulsion liquid dosage form for external application to the skin
20
Q
what is a gel
A
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
21
Q
what is a topical suspension
A
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
22
Q
what is a topical solution
A
A clear homogeneous liquid dosage form for external application to the skin
23
Q
what are the types of non-water washable bases
A
Oleaginous/Hydrocarbon bases
Absorption bases
Water in oil (W/O) emulsion bases
Silicone bases
24
Q
what is an occlusion
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)
25
what are properties of Oleaginous/Hydrocarbon bases
* Hydrophobic
* Greasy
* Non-water washable
* Occlusive
* Emollient
26
what are advantages of Oleaginous/Hydrocarbon bases
Very stable vehicles
Non-irritating
Non-sensitizing
High compatibility with drugs
27
what are disadvantages of Oleaginous/Hydrocarbon bases
Greasiness
Stain clothing
Difficult to remove
Low patient acceptance
28
examples of excipients in Oleaginous/Hydrocarbon bases
1. fats and fixed oils - susceptible to oxidation, become rancid (ex. vegetable oils)
2. waxes - stiffening agents (increase viscosity) - (ex. white wax, hard paraffin)
29
Vehicles in Oleaginous/Hydrocarbon bases
1. petrolatum, white petrolatum (greasy, high mp)
| 2. plastibase/oleo-gel (greasy, stains, lower mp, drugs released faster than petrolatum)
30
What are properties of absorption bases
Hydrophobic
Greasy
Anhydrous; hydrophilic components provide water- absorbing properties
Upon water addition form W/O emulsions
31
Examples of absorption bases
1. anhydrous lanolin/wool fat (takes up 2x its weight in water)
2. lanolin/hydrous wool fat (takes up limited amounts of water)
32
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
33
Examples of W/O emulsions
1. Cold creams (beeswax-borax system- in situ emulsifier)
| 2. Emollient creams (Rose water ointment, USP)
34
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
35
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%
```
36
What are the types of water washable bases
O/W emulsions
Gels
Hydrophilic bases
Emulsifying base
37
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
38
What is vanishing cream
* Stearic acid and KOH form potassium stearate in situ
* Smooth, easy to apply
* Instantaneous absorption to the skin
* No residue
39
What are gels
two-component (liquid and polymer) colloidal system
40
what are gel-forming materials
* Natural gums: tragacanth, agar, pectin, alginates
* Semi-synthetic or synthetic polymers: methylcellulose, hydroxymethylcellulose, hydroxypropylcellulose,
* Synthetic polymers: carbopol
* Clays: bentonite
41
Properties of gels
- Dissolve in water
| - Good for hairy areas
42
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)
43
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
44
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
45
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
46
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
47
What are examples of permeation enhancers
Fatty acids (Oleic acid)
Alcohols, glycols (ethanol, propylene glycol)
Surfactants (SDS, Tween 80)
Urea
48
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
```
49
How to determine which formulation to be used on skin
Chart on page 49
50
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
51
What is the therapy for acne
- Bacteriostatics: benzoyl peroxide
- Topical antibiotics
- Exfoliants: sulfur, resorcinol, tretinoin, salicylic acid, benzoyl peroxide
52
What bases are used for acne
- liquids (water or alcohol based)
- gels
- creams, o/w emulsions
- Do NOT use occlusive bases
53
Pathophysiology of alopecia
Natural or abnormal loss of hair on the scalp
| - family history, androgenic influences, aging, systemic disorders
54
What are the types of alopecia
Alopecia totalis → no hair
| Alopecia areata → patchy hair loss
55
Treatment of alopecia
No satisfactory treatment (possibly Minoxidil/Rogaine)
56
Types of bases used for alopecia
- water or alcohol based liquids
- gels
- creams
57
Pathophysiology of dermatitis (eczema)
Superficial inflammation of the skin.
Types:
- atopic dermatitis (allergic condition)
- contact dermatitis (delayed hypersensitivity reaction)
58
What is the treatment used for dermatitis
Emollients
Astringents
Antipruritics
Topical corticosteroids
59
Types of bases used for dermatitis
creams
lotions
try to avoid occlusion
60
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
61
Treatment of psoriasis
Emollients (hydration)
Keratolytics (remove scales)
Corticosteroids (treat inflammation)
62
Types of bases used for psoriasis
occlusive (the more the better) → hydrocarbons, silicon bases
creams
ointments with plastic wrap (↑ hydration)
63
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
64
What is the treatment for urticaria
Topical astringents
Anti-inflammatory lotions
Anti-histamines
65
Types of bases used for urticaria
non-occlusive
gels
shake lotions (cool — relieve burning and itching)
creams
66
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
67
Treatment of Herpes Simplex
Topical antiviral preparations
| Lotions containing camphor and tannic acid
68
Types of bases used for herpes simplex
non-occlusive
liquid lotions
PEG
gels
69
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.
70
Therapy for corns and calluses
Remove causative factor
Keratolytics (salicylic acid > 10%, resorcinol)
Caustics (lactic acid, trichloroacetic acid emulsions)
Emollients
71
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)
72
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
73
Therapy for athlete's foot
Thoroughly dry feet after shower/bath.
Antifungal powders
Topical antifungal creams
74
What types of bases are used for athlete's foot
non-occlusive
| o/w creams
75
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
76
What is the parent molecule of most corticosteroids
Hydrocortisone (it's not very potent so modifying structure increases its potency)
77
How does concentration affect absorption of topical corticosteroids
Higher concentrations will increase the potency
78
How does hydration affect absorption of topical corticosteroids
Application to hydrated skin after bathing can increase absorption 4-5 fold
79
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)
80
How are topical corticosteriods classified
classified according to their relative potencies. (Class I = ultra high potency and Class VII = lowest potency)
81
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
82
Medium to high potency (Classes II-V) topical corticosteroids
- Used for mild to moderate nonfacial and nonintertriginous areas
83
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
84
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
```
85
What is the order of potency for different formulations
ointment>cream>lotion>gel>foam/spray/ solution
85
What is the order of potency for different formulations
ointment>cream>lotion>gel>foam/spray/ solution
86
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
87
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
88
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
89
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
90
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
91
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
92
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
```
93
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
94
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
95
How often should topical corticosteroids be applied
- can be applied OD to QID, but OD-BID is preferred to reduce risk of side effects
96
What does "apply sparingly" mean
Clarify that “It is important to apply just enough to cover the affected area”
97
What is the fingertip unit (FTU)
1 FTU = 1/2 g (500mg) = treats 2% BSA
| 1 palm = 1% BSA (patients palm)
98
What is the rule of hand
4 hand areas = 2 FTU = 1 g cream
99
What is the rate limiting factor for diffusion across the skin
the stratum corneum
100
How does Fick's Law apply to drug permeation across the skin
concentration gradient determines diffusion properties
101
Where do highly hydrophobic drugs from a depot
in the stratum corneum or in the dermis (ex. corticosteroids)
102
What is the target delivery site of topical formulations vs. transdermal therapeutic systems
topical: target = skin
patch: target = systemic system
103
what are the routes for percutaneous absorption
1. across the stratum corneum - brick and mortar model (bricks = protein/cells, mortar = lipid)
2. via appendages (Sweat ducts, Sebaceous glands, Hair follicles)
104
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)
105
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
106
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)
