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Pharm 124 > Semi-solids > Flashcards

Semi-solids Flashcards

1
Q

what is the largest organ in the body

A

the skin

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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
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3
Q

what is the pH of the skin

A

5.5 (acid mantle)

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4
Q

what is the thickness of the epidermis

A

average: 200 μm
palms and soles: 800 μm
eyelid: 60 μm

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5
Q

what is the thickness of the dermis

A

1-5 mm

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6
Q

what are the layers of the epiderms

A 
stratum corneum 
stratum lucidum
stratum granulosum
stratum spinosum
stratum basale
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7
Q

Which layer of the skin is the site for drug metabolism

A

dermis

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8
Q

what products target the skin surface

A

cosmetics
protective films (sunscreens)
antifungal/antibacterial (ex. polysporin)

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9
Q

what products target the stratum corneum

A

emollients and moisturizers (increase water content)

keratolytics (remove dead cells)

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10
Q

what products target skin appendages

A 
antiperspirants (aluminum salts)
exfoliants (salicylic acid, tretinoin)
depilatories
antibiotics 
antifungals
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11
Q

what products target the epidermis/dermis

A

anti-inflammatory agents
local anesthetics
antihistamines
anticancer drugs

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12
Q

what products target percutaneous absorption (systemic treatment)

A

motion sickness (scopolamine)
angina (nitroglycerin)
hypertension (clonidine)
smoking cessation (nicotine)

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13
Q

What are the types of dermatological vehicles

A 
ointments
creams/lotions
pastes
gels
aerosols
powders
liquids
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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

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15
Q

What are the types of vehicles based on WASHABILITY

A

non-water washable

water washable

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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

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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

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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

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19
Q

what is a lotion

A

An emulsion liquid dosage form for external application to the skin

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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

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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

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22
Q

what is a topical solution

A

A clear homogeneous liquid dosage form for external application to the skin

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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

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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)

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25
Q

what are properties of Oleaginous/Hydrocarbon bases

A
  • Hydrophobic
  • Greasy
  • Non-water washable
  • Occlusive
  • Emollient
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26
Q

what are advantages of Oleaginous/Hydrocarbon bases

A

Very stable vehicles
Non-irritating
Non-sensitizing
High compatibility with drugs

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27
Q

what are disadvantages of Oleaginous/Hydrocarbon bases

A

Greasiness
Stain clothing
Difficult to remove
Low patient acceptance

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28
Q

examples of excipients in Oleaginous/Hydrocarbon bases

A
  1. fats and fixed oils - susceptible to oxidation, become rancid (ex. vegetable oils)
  2. waxes - stiffening agents (increase viscosity) - (ex. white wax, hard paraffin)
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29
Q

Vehicles in Oleaginous/Hydrocarbon bases

A
  1. petrolatum, white petrolatum (greasy, high mp)

2. plastibase/oleo-gel (greasy, stains, lower mp, drugs released faster than petrolatum)

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30
Q

What are properties of absorption bases

A

Hydrophobic
Greasy
Anhydrous; hydrophilic components provide water- absorbing properties
Upon water addition form W/O emulsions

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31
Q

Examples of absorption bases

A
  1. anhydrous lanolin/wool fat (takes up 2x its weight in water)
  2. lanolin/hydrous wool fat (takes up limited amounts of water)
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32
Q

Properties of W/O emulsions

A

More greasy than O/W emulsions
Emollient, cleansing action
Capable of absorbing oil-soluble compounds from the skin e.g. make-up removers

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33
Q

Examples of W/O emulsions

A
  1. Cold creams (beeswax-borax system- in situ emulsifier)

2. Emollient creams (Rose water ointment, USP)

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34
Q

Properties of pastes

A

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

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35
Q

Properties of silicon bases

A 
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%
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36
Q

What are the types of water washable bases

A

O/W emulsions
Gels
Hydrophilic bases
Emulsifying base

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37
Q

Properties of O/W emulsions

A

Water washable
Soft
Non-occlusive
Moisturizing (increases water content -> restores hydration of the skin)
Penetration enhancement of the drug compounds

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38
Q

What is vanishing cream

A
  • Stearic acid and KOH form potassium stearate in situ
  • Smooth, easy to apply
  • Instantaneous absorption to the skin
  • No residue
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39
Q

What are gels

A

two-component (liquid and polymer) colloidal system

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40
Q

what are gel-forming materials

A
  • Natural gums: tragacanth, agar, pectin, alginates
  • Semi-synthetic or synthetic polymers: methylcellulose, hydroxymethylcellulose, hydroxypropylcellulose,
  • Synthetic polymers: carbopol
  • Clays: bentonite
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41
Q

Properties of gels

A
  • Dissolve in water

- Good for hairy areas

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42
Q

Properties of hydrophilic bases

A
  • 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)
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43
Q

Properties of emulsifying bases (ointment)

A

Anhydrous bases containing O/W emulsifying agents
Miscible with water
Self-emulsifying (does not need excipients)
Cream-like appearance
Water- washable

44
Q

What is a levigating agent

A

• 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
Q

What is a penetration enhancer

A

• Temporarily increase the permeability of the skin to allow drug molecules to pass
eg,. chemical permeation enhancers, specialized delivery systems

46
Q

What are properties of an ideal penetration enhancer

A
  • 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
Q

What are examples of permeation enhancers

A

Fatty acids (Oleic acid)
Alcohols, glycols (ethanol, propylene glycol)
Surfactants (SDS, Tween 80)
Urea

48
Q

Examples of antimicrobial preservatives

A 
Alcohols: ethanol, isopropanol
Acids: benzoic acid
Mercurials: thimerosal
Phenols: phenol, cresol
p-hydroxybenzoates: methyl-, propyl-, butylparaben Quaternary ammonium compounds: benzalkonium chloride, cetrimide
49
Q

How to determine which formulation to be used on skin

A

Chart on page 49

50
Q

What is the pathophysiology of acne

A
  • 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
Q

What is the therapy for acne

A
  • Bacteriostatics: benzoyl peroxide
  • Topical antibiotics
  • Exfoliants: sulfur, resorcinol, tretinoin, salicylic acid, benzoyl peroxide
52
Q

What bases are used for acne

A
  • liquids (water or alcohol based)
  • gels
  • creams, o/w emulsions
  • Do NOT use occlusive bases
53
Q

Pathophysiology of alopecia

A

Natural or abnormal loss of hair on the scalp

- family history, androgenic influences, aging, systemic disorders

54
Q

What are the types of alopecia

A

Alopecia totalis → no hair

Alopecia areata → patchy hair loss

55
Q

Treatment of alopecia

A

No satisfactory treatment (possibly Minoxidil/Rogaine)

56
Q

Types of bases used for alopecia

A
  • water or alcohol based liquids
  • gels
  • creams
57
Q

Pathophysiology of dermatitis (eczema)

A

Superficial inflammation of the skin.
Types:
- atopic dermatitis (allergic condition)
- contact dermatitis (delayed hypersensitivity reaction)

58
Q

What is the treatment used for dermatitis

A

Emollients
Astringents
Antipruritics
Topical corticosteroids

59
Q

Types of bases used for dermatitis

A

creams
lotions
try to avoid occlusion

60
Q

What is psoriasis and how does it look

A

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
Q

Treatment of psoriasis

A

Emollients (hydration)
Keratolytics (remove scales)
Corticosteroids (treat inflammation)

62
Q

Types of bases used for psoriasis

A

occlusive (the more the better) → hydrocarbons, silicon bases
creams
ointments with plastic wrap (↑ hydration)

63
Q

What is Urticaria and what does it look like

A

A vascular reaction to insect bites, diet or drugs.

  • wheals surrounded by a halo accompanied
    by severe itching and burning
64
Q

What is the treatment for urticaria

A

Topical astringents
Anti-inflammatory lotions
Anti-histamines

65
Q

Types of bases used for urticaria

A

non-occlusive
gels
shake lotions (cool — relieve burning and itching)
creams

66
Q

What is Herpes Simplex and what does it look like

A

Recurrent viral infection of the skin and mucous membranes.

  • vesicles appearing in clusters on erythematous base — associated with tingling and itching
67
Q

Treatment of Herpes Simplex

A

Topical antiviral preparations

Lotions containing camphor and tannic acid

68
Q

Types of bases used for herpes simplex

A

non-occlusive
liquid lotions
PEG
gels

69
Q

What are corns and calluses and what do they look like

A

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
Q

Therapy for corns and calluses

A

Remove causative factor
Keratolytics (salicylic acid > 10%, resorcinol)
Caustics (lactic acid, trichloroacetic acid emulsions)
Emollients

71
Q

Types of bases used for corns and calluses

A

occlusive - the more the better (easier to remove by abrasion)
collodions (liquid with organic solvents + polymer that deposits on skin)

72
Q

What is athlete’s foot and what does it look like

A

Superficial fungal infection of the skin.
- small blisters between toes (blisters may break and become hard and scaly), cracks, redness, maceration, itching, burning

73
Q

Therapy for athlete’s foot

A

Thoroughly dry feet after shower/bath.
Antifungal powders
Topical antifungal creams

74
Q

What types of bases are used for athlete’s foot

A

non-occlusive

o/w creams

75
Q

What are topical corticosteroids?

A
  • 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
Q

What is the parent molecule of most corticosteroids

A

Hydrocortisone (it’s not very potent so modifying structure increases its potency)

77
Q

How does concentration affect absorption of topical corticosteroids

A

Higher concentrations will increase the potency

78
Q

How does hydration affect absorption of topical corticosteroids

A

Application to hydrated skin after bathing can increase absorption 4-5 fold

79
Q

What factors influence topical corticosteroids absorption kinetics

A
  • concentration
  • hydration
  • occlusion
  • penetration enhancers (propylene glycol, urea, salicylic acid)
  • mixing of bases (can increase or reduce potency)
80
Q

How are topical corticosteriods classified

A

classified according to their relative potencies. (Class I = ultra high potency and Class VII = lowest potency)

81
Q

Super/Ultra high potency (Class I) topical corticosteroids

A
  • 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
Q

Medium to high potency (Classes II-V) topical corticosteroids

A
  • Used for mild to moderate nonfacial and nonintertriginous areas
83
Q

Lower potency (Class VI and VII) topical corticosteroids

A
  • 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
Q

Can the same topical corticosteriod be in different classes

A 
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
Q

What is the order of potency for different formulations

A

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

85
Q

What is the order of potency for different formulations

A

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

86
Q

When should ointments be chosen as the vehicle for topical corticosteriods

A
  • 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
Q

When should creams be chosen as the vehicle for topical corticosteriods

A
  • 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
Q

When should lotions be chosen as the vehicle for topical corticosteriods

A
  • 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
Q

When should gels be chosen as the vehicle for topical corticosteriods

A
  • 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
Q

When should foams, sprays or solutions be chosen as the vehicle for topical corticosteriods

A
  • 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
Q

what are local side effects of topical corticosteroids

A

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
Q

What are systemic side effects of topical corticosteroids

A 
- Hypothalamic-pituitary axis suppression -
Cushing’s syndrome
- hyperglycemia
- growth retardation in children
- Glaucoma (when applied to eyelid) 
- Hypertension
93
Q

How to limit side effects of topical corticosteroids

A
  • 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
Q

How to prevent tolerance (tachyphylaxis) of topical corticosteroids

A

can be prevented by limiting the long term application to once or twice daily or by stopping the therapy for a few days

95
Q

How often should topical corticosteroids be applied

A
  • can be applied OD to QID, but OD-BID is preferred to reduce risk of side effects
96
Q

What does “apply sparingly” mean

A

Clarify that “It is important to apply just enough to cover the affected area”

97
Q

What is the fingertip unit (FTU)

A

1 FTU = 1/2 g (500mg) = treats 2% BSA

1 palm = 1% BSA (patients palm)

98
Q

What is the rule of hand

A

4 hand areas = 2 FTU = 1 g cream

99
Q

What is the rate limiting factor for diffusion across the skin

A

the stratum corneum

100
Q

How does Fick’s Law apply to drug permeation across the skin

A

concentration gradient determines diffusion properties

101
Q

Where do highly hydrophobic drugs from a depot

A

in the stratum corneum or in the dermis (ex. corticosteroids)

102
Q

What is the target delivery site of topical formulations vs. transdermal therapeutic systems

A

topical: target = skin
patch: target = systemic system

103
Q

what are the routes for percutaneous absorption

A
  1. across the stratum corneum - brick and mortar model (bricks = protein/cells, mortar = lipid)
  2. via appendages (Sweat ducts, Sebaceous glands, Hair follicles)
104
Q

What are the drug factors influencing percutaneous absorption

A
  • 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
Q

What are the vehicle factors influencing percutaneous absorption

A
  • 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
Q

What are the skin factors influencing percutaneous absorption

A
  • 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)

Pharm 124 (4 decks)

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