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PHAR 224 > Dermatologicals > Flashcards

Dermatologicals Flashcards

1
Q

What are main layers of the skin?

A
  1. Epidermis
  2. Dermis
  3. Subcutaneous tissue
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2
Q

What are the layers of the epidermis?

A

Stated from outermost to innermost layer

  1. Stratum corneum
  2. Stratum lucidum
  3. Stratum granulosum
  4. Stratum spinosum
  5. Stratum basale
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3
Q

Does the epidermis have a blood supply?

A

No

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4
Q

Does the dermis have a blood supply?

A

Yes, it is also innervated. Both are important for drug delivery

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5
Q

What layer of the skin attaches to the underlying muscles?

A

Subcutaneous

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6
Q

What are some characteristics of the epidermis?

A

Fairly thin, but thickest on the palms and soles

Basic pH (5.5) anti-microbial

Made from keratinocytes (synthesize keratin), melanocytes, and dendritic Langerhans cells (involved in immune signalling)

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7
Q

What are some characteristics of the stratum corneum?

A

10-15 layers of flattened aneucleated cells

Undergoes desquamation

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8
Q

What are the main functions of the stratum corneum?

A
  1. Main permeability barrier of the skin
  2. Controls percutaneous absorption
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9
Q

What is desquamation?

A

A process in which the top layers of the stratum corneum are shed away from the skin.

This is a normal process

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10
Q

What are some characteristics of the stratum lucidum?

A

Flattened, anucleated cells

Cytoplasm is fulled with filaments that allow for the skin to stretch

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11
Q

What are the main functions of the stratum lucidum?

A
  1. Responsible for the skin’s ability to stretch
  2. Contains a protein that is responsible for the degeneration of skin cells
  3. Lowers the effects of friction on the skin (especially in the soles and palms)
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12
Q

What are some characteristics of the stratum granulosum?

A

First layer of living cells (and first point where drugs start to interact with the body’s biochemistry (pro-drug into drug))

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13
Q

What is the main function of the stratum granulosum?

A

It is the site of biochemical activity (drugs can be activated or inactivated)

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14
Q

What are some characteristics of the stratum spinosum?

A

Contain prickly filaments that are subject to constant pressure and friction

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15
Q

What is the main function of the stratum spinosum?

A

Helps the skin resist abrasion

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16
Q

What are some characteristics of the stratum basale?

A

Last layer of epidermis

First layer of nucleated basal cells (undergo mitosis)

Turnover time of 28 days

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17
Q

What is the main function of the stratum basale?

A

Provides the germinal cells necessary for the regeneration of the layers of the epidermis

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18
Q

What are the most significant differences between the epidermis and dermis?

A

The dermis contains vascular and neurological supply, while the epidermis does not

The dermis also where follicles root themselves, with the hairshaft growing through the epidermis

The dermis also allows for vasocontriction and dilation to help with heat control

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19
Q

What are the main functions of the dermis?

A
  1. Supports the epidermis
  2. Thermoregulation (vasoconstriction/dilation)
  3. Aid in sensation
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20
Q

What is the pH of the dermis?

A

pH 7.2, closer to physiological ranges

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21
Q

What is the significance of the pH difference between the epidermis and dermis?

A

Epidermis pH: 5.5

Dermis pH: 7.2

Topically applied drugs should be stable within these pH ranges

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22
Q

What are the functions of the subcutaneous tissue?

A
  1. Storing energy/insulation (due to fat deposits)
  2. Connects the dermis (& epidermis) to the muscles and bones
  3. Serves as a mechanical cushion
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23
Q

What happens to the subcutaneous tissue as we age?

A

It starts to decrease in size, causing the skin above to sag

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24
Q

What are some challenges presented by the epidermis to drug delivery?

A

The stratum corneum is the major rate-limiting barrier to transdermal drug delivery

Topical agents are subject to the enzymatic activation or deactivation of drugs as they pass through the stratum germinativum.

Immune cells present in the epidermis can also destroy active ingredients

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25
Q

What are the advantages of subcutaneous administration vs. IM?

A

Subcutaneous tissue has fewer blood vessels, allowing for a more gradual rate of absorption (depot effect)

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26
Q

What happens to a topical drug once it reaches the dermis?

A

It can be absorbed into the systemic circulation

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27
Q

What are some frequently treated skin conditions?

A
  1. Acne
  2. Cold Sores
  3. Dermatitis
  4. Common warts
  5. Psoriasis
  6. Tinea capitis
  7. Photoallergic reactions
  8. Fungal skin infections
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28
Q

What are some important aspects that must be considered when developing a topical dosage form?

A
  1. Pathophysiology of the disease condition
  2. Active ingredient characteristics
  3. Intended therapy (localized vs. systemic)
  4. Vehicle/drug delivery system
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29
Q

What are some physicochemical criteria for a good topical dosage form?

A
  1. Stability of active ingredient and adjuvants
  2. Consistency and extrudability
  3. Prevention of water loss or volatile compounds
  4. Phase changes (homogeneity, phase separation)
  5. Particle size and distribution of the dispersed phase
  6. Apparent pH
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30
Q

What are some factors that affect drug bioavailability in topical dosage forms?

A
  1. Skin disease or condition
  2. Rate of drug release
  3. Promotion of percutaneous absorption
  4. Requirement for occlusion
  5. Short- and long-term stability of the drug in ointment base
  6. Influence of the drug on the consistency of the base
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31
Q

What are the different types of ointment bases?

A
  1. Hydrocarbon bases
  2. Absorption bases
  3. Emulsifying bases
  4. Water soluble bases
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32
Q

What are the different types of creams?

A

Oil in water (O/W) emulsions

Water in oil (W/O) emulsions

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33
Q

What is the definition of an ointment?

A

Contains less than 20% water and volatiles, and more than 50% of hydrocarbons, waxes, or polyethylene glycols

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34
Q

What is the definition of a cream?

A

An emulsion semi-solid dosage form that contains more than 20% water and volatiles, and less than 50% of hydrocarbons, waxes, or polyethylene glycols

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35
Q

What are some characteristics of ointments?

A

Semi-solid greasy preparations

Mostly anhydrous, but may contain dissolve or dispersed active pharmaceutical ingredient (API)

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36
Q

What are some charcteristics of creams?

A

Semi-solid preparations that contain both oil phase and water

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37
Q

What is the main distinction between ointments and creams?

A

Ointments have little amounts of water, unlike creams. Creams have a varying amounts of water

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38
Q

How can dermatological vehicles (bases) be divided into two main groups?

A
  1. Non water-washable bases
  2. Water washable vehicles
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39
Q

Which dermatological bases are non water-washable bases?

A
  1. Oleaginous/Hydrocarbon bases
  2. Absorption bases
  3. Water in oil (W/O) emulsions
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40
Q

Which dermatological bases are water washable vehicles?

A
  1. Oil in water (O/W) emulsions
  2. Gels
  3. Hydrophillic base
  4. Emulsifying base
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41
Q

Review slide 41 for a review of dermatological bases

A
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42
Q

Review slide 42 for modification of dermatological bases

A
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43
Q

What are some properties of Oleaginous bases?

A
  1. Hydrophobic
  2. Greasy
  3. Non-water washable
  4. Occlusive
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44
Q

What is occlusion?

A

It is formation of an impermeable layer on the skin to prevent evaporation of water

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45
Q

What are the benefits of good occlusive character?

A
  1. Increased hydration (prevent evaporation of water from skin)
  2. Enhanced percutaneous absorption due to increased retention on skin
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46
Q

Are oleaginous bases preferred for widespread use on the skin?

A

Despite its good occlusive charcacter, it is too much of a good thing for application on large areas

Oleaginous bases can be too greasy and are uncomfortable

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47
Q

What are some advantages of oleaginous bases?

A
  1. Very stable vehicles
  2. Non-irritating
  3. Non-sensitizing
  4. High compatibility with drugs
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48
Q

What are some the disadvantages of oleaginous bases?

A
  1. Greasiness
  2. Stain clothing
  3. Difficult to remove
  4. Low patient acceptance (emulsion bases are more preferred)
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49
Q

What are some common ingredients of oleaginous bases?

A
  1. Fats and fixed oils
  2. Penetration enhancers
  3. Levigating agent
  4. Antimicrobial preservatives (not commonly used in extemporaneous compounding)
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50
Q

What is the mechanism of action of penetration enhancers?

A

Fluidization of stratum corneum lipids. This increases the permeability and absorption of drug into skin

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51
Q

What is the purpose of a levigating agent?

A

They are liquids used as an intervening agent to aid the incorporation and particle size reduction of a powder into an ointment

ex. Mineral oil

52
Q

What are the two compounding methods for topical dosage forms?

A
  1. Fusion (melt)
  2. Incorporation
53
Q

What is the process for fusion compounding methods for topical dosage forms?

A
  1. Components are melted together
  2. Cooled with constant stirring until congealed
54
Q

When using the fusion compounding method, should the temperature be set to the lowest or highest melting points?

A

It really does not matter, but starting from lower temperature to higher is the most common method

Ensure temperatures do not exceed smoking points of any base involved

55
Q

What is the process for incorporation compunding method for topical dosage forms?

A

Mix one semi-solid formulation into another via geometric dilution

  1. In a mortar with pestle
  2. On a slab with spatula
56
Q

Can fusion and incorporation compunding methods be combined?

A

Yes

Order of steps:

  1. Fusion
  2. Incorporation
57
Q

What are some relevant beyond-use-dates (BUDs) for extemporaneously compounded topical dosage forms?

A
  1. Non-preserved aqueous: 14 days
  2. Preserved aqueous: 35 days
  3. Nonaqueous dosage forms: 90 days
58
Q

How are absorption bases formed?

A

Adding a W/O emulsifier to an oleaginous base

59
Q

What are some characteristics of absorption bases?

A

They contain oleaginous material and a water-in-oil (W/O) emulsifier so that they can absorb water to form or expand w/o emulsions

60
Q

What are some distinct applications of absorption bases?

A

They are used in oozing conditions because they are not easily removed with water.

Absorption bases can also pull fluids from a wound, especially important in preventing infections in recovery

61
Q

What are the main components of absorption bases?

A

Very similar to oleaginous bases (fats, mineral oil, petrolatum, waxes), but also include w/o emulsifying agent

62
Q

What are the two main types of absorption bases?

A

Type 1 (Anhydrous bases)

Type 2 (Lanolin)

63
Q

What are some qualities of a Type 1 absorption base?

A

Type 1 absorption bases are used for specialty compunding for drugs like HRT

ex. Cholesterol

64
Q

What are some qualities of a Type 2 absorption base?

A

Type 2 (Lanolin) can take up to two times its weight of water

Acts as W/O emulsifier

65
Q

What are some additional additives for absorption bases?

A
  1. Antioxidants
  2. Penetration enhancers
66
Q

What are some desired characteristics for antioxidants in absorption bases?

A
  1. Effective at low concentrations
  2. Soluble in vehicle
  3. Compatible with pharmaceutical excipients and wide range of drugs
  4. Odourless, tasteless
67
Q

What are some examples of perservatives used in absorption bases?

A

Extemporaneously Compounded:
butylated hydroxy toluene (BHT) and butylated hydroxy anisole (BHA)

Commercial preparations:
alpha-tocopherol

68
Q

Can hydrophillic levigating agents be used in absorption bases?

A

Yes, both hydrophobic and hydrophillic levigating agents can be also be used in absorption bases

69
Q

What are qualities of emulsifying bases?

A

Also known as water-washable base

They are anhydrous bases containing o/w emulsifying agents

Cream-like appearance
Muscible with water

Precursor of o/w emulsions (need to add water to emulsifying bases)

70
Q

What are the components of emulsfying bases?

A

Very similar to oleaginous bases (fats, mineral oil, petrolatum, waxes), but also contain o/w emulsifiers and other surfactants

71
Q

What is the common compounding method for emulsifying agents?

A

Fusion method is more commonly applied

72
Q

What types of levigating agents are used in emulsfying bases?

A

Both hydrophillic and hydrophobic agents can be used

Emulsfying bases themselves can be used as a levigating agent in most final formulations

73
Q

What are the two types of creams?

A

W/O emulsion

O/W emulsion

74
Q

What are some qualities of w/o emulsions?

A
  1. Greasier than O/W emulsions
  2. Non-water washable
  3. Emollient
  4. Capable of absorbing oil-soluble compunds from the skin
75
Q

What are some qualities of o/w emulsions?

A
  1. Water washable
  2. Non-occlusive
  3. Moisturizing

O/W emulsions are more commonly seen as medicated creams (allow higher penetration of drug compounds)

76
Q

What are some common additives for emulsions?

A
  1. Antioxidants (available for oil and water phases)
  2. Penetration enhancers
  3. Preservatives (due to water content)
  4. Humectants (helps retain water content, prolonging shelf life)
77
Q

What are the most common preservatives used in emulsions?

A

Parabens (use is growing)

78
Q

Are humectants found in high concentrations in emulsions?

A

No, they are at low concentrations and work as intended at these concentrations

Humectants negate their desired effects, if their concentration is too high

ex. PEG

79
Q

What are the main methods of compounding a cream base?

A
  1. Fusion
  2. Incorporation
80
Q

How is the fusion method used to form cream bases?

A

This method is preferred when a cream base from scratch is desired

  1. Fusion of hydrophobic components
  2. Add hydrophillic component (heated to 5*C hotter than oil phase)
  3. Water phase added to oil phase gradually with constant stirring until fully cooled and congealed
81
Q

How is the incorporation method used to form cream bases?

A

Commonly performed with commercial bases

Mix one semi-solid formulation into another (usually on glass plate)

82
Q

Need to add lotion flashcards

A
83
Q

What is the definition of a paste in a pharmacology sense?

A

An oleaginous that contains 20% or more solids suspended in the base

84
Q

What are some qualities of a paste?

A

Very stiff consistency

Form a thick impermeable layer on the skin

ex. Oracort

85
Q

Should pharmacists use mortar and pestle to levigate pastes?

A

No, use glass slab for incorporation

86
Q

What are some properties of hydrophillic bases?

A
  1. They contain water-washable components
  2. Non-oclussive
  3. Non-irritant
  4. Cannot take up more than 8% water
87
Q

What are some incompatible ingredients seen in hydrophillic bases?

A
  1. Phenols, iodine, KI, tannic acid, silver
  2. Reduce the antimicrobial actvity of quartenary compounds and parabens
  3. Inactviate bacitracin, pencillin
88
Q

What are the advantages of hydrophillic bases?

A
  1. Anhydrous (useful for drugs that hydrolyze
  2. Good patient compliance (non-staining and non-occlusive)
89
Q

What are some qualities of gels?

A
  1. Water washable bases
  2. Liquid-rich, two-compartment
  3. Natural and synthetic polymers that from form a 3D matrix
  4. Good for hairy areas
90
Q

Can gels be used on dry skin?

A

No, it has poor moisture barrier

91
Q

How are gels compounded (Carbomer)?

A
  1. Measure/weight ingredients
  2. Dissolve water-soluble ingredients in water in a beaker
  3. Sprinkle carbomer (gelling agent) on to the liquid surface and vigourously stir
  4. Needed to adjust pH, because carbomer can create a very acidic environment
  5. Qs with water if needed
92
Q

What is percutaneous absorption?

A

It is the amount of drug that passes from the vehicle into the stratum corneum of the skin

93
Q

How does the skin act as a passive barrier for topical drug absorption?

A

The skin allows movement of drug from high to low concentration and prevents movement in the opposite direction due to concentration gradient

Diffusion across the stratum corneum is the rate-limiting step in topical drug absorption

94
Q

What are the routes of percutaneous absorption?

A
  1. Across stratum corneum
  2. Via appendages
95
Q

What are the two routes for percutaneous absorption across the strateum corneum?

A

Intracellular route (pass through multiple cells)

Intercellular route (drug passes around skin cells through the stratum corneum)

96
Q

How is drug percutaneously absorbed via appendages?

A

Negligible process, but more pronounced for microbial actvity

Drug enters through sweat ducts, sebaceius glands, and hair follicles

97
Q

What are some factors that affect percutaneous absorption?

A
  1. Drug factors
  2. Vehicle factors
  3. Skin factors
98
Q

How do drug factors affect percutaneous absorption?

A

Concentration of drug in the preparation needs to be sufficient to provide a high concentration gradient

Partition coefficient (ratio of drug concentration between stratum corneum to the vehicle)

99
Q

How do vehicle factors affect percutaneous absorption?

A
  1. pH (determines ionization of drug)
  2. Co-solvents (define concentration of drug on skin surface)
  3. Release of drug from vehicle (different for ointment vs. cream)
  4. Penetration enhancers (increased permeability)
100
Q

Do corticosteroid ointments have lower potency vs. corticosteroid creams?

A

No, corticosteroid ointments have higher potency vs. creams of the same active ingredient

Difference is due to increased occulsive factor of ointments

101
Q

What skin factors affect percutaneous absorption?

A
  1. Age of the skin
  2. Skin condition
  3. Stratum corneum thickness
  4. Skin metabolism
  5. Circulation effects
  6. Species differences (important in animal testing)
102
Q

What are the most accurate animal models for studying percutaneous absorption?

A
  1. Pigs (closest to human)
  2. Guinea pigs
  3. Hairless mouse
103
Q

What is the blanching test?

A

Human volunteers are used to qualitatively assess topical availability and potency of corticosteroids.

Skin whitening after corticosteroid application correlates directly with the topical availability of the drug

104
Q

What does Fick’s Law describe?

A

Fick’s Law relates the rate diffusion of a substance across a membrane to be proportional with concentration gradient

Review slide 133

105
Q

What is the equation of Fick’s Law?

A

J = (D x P/δ) x Δ[drug]

J = solute flux (cumulative diffusion in unit time)

D = solute diffusion coefficient

P = solute partition coefficent (drug concentration in skin/drug concentration in vehicle)

δ = thickness of stratum corneum

Δ[drug] = (drug concentration in vehicle - drug concentration in skin)

Know the variables and their relationship with J (solute flux)

106
Q

Why is drug concentration elevated at the skin’s surface?

A

As the drug falls out of the vehicle (donor compartment), it’s absorption is limited by the stratum corneum. This causes drug to build up on the skin’s surface as it slowly diffuses into deeper parts of the skin (receptor compartment)

107
Q

Why does drug concentration rapidly fall when leaving the skin and entering the receptor compartment?

A

This phenomenon is also known as the Sink effect

The drug does not stay at the interface of skin and receptor compartment and partitions into deeper parts of tissue

108
Q

What is the utility of Fick’s Law?

A

Drug concentration can be easily ascertained in the donor and receptor compartments, but it is near impossible to measure drug concentration at the interfaces

Knowing interface drug concentration allows med chemists to figure out donor compartment concentration that could drive a concentratin gradient that delivers an appropriate amount of drug into the receptor compartment

109
Q

What is the diffusion coefficient of the drug?

A

The amount of drug that diffuses across a unit area of the stratum corneum in 1 second due to the concentration gradient (indirect measure of membrane permeability)

110
Q

What is partition coefficient?

A

Ratio of drug concentration in Phase A (vehicle) to the concentration in Phase B (stratum corneum)

111
Q

What is the permeability coefficient?

A

A measure of the rate at which a molecule can cross a membrane

112
Q

What is the equation for permeability coefficient?

A

Kp = D x P/δ

D = solute diffusion coefficient

P = solute partition coeffient (drug concentration in skin/drug concentration in vehicle)

δ = thickness of stratum corneum

Do not memorize equation, instead know general relationships

113
Q

Is a smaller partition coefficient responsible for better penetration?

A

False

Greater partition coefficient = more drug into skin = better penetration

114
Q

What is the main difference between dermal and transdermal formulations?

A

They are both topical dosage forms, but drug in transdermal formulation is intended to pass through the skin and enter the systemic circulation

115
Q

What are the target regions for topical formulations?

A
  1. Skin surface and stratum corneum
  2. Viable epidermis and dermis
  3. Skin Appendages
  4. Systemic Treatment
116
Q

What types of preparations target the stratum corneum?

A
  • Emollients and moisturizers
  • Protective films (ex. sunscreen)
  • Topical Antibiotics
  • Keratolytics
117
Q

What types of preparations target the epidermis and dermis?

A
  • Topical NSAIDs
  • Local anesthetics
  • Anti-histamines
  • Anti-cancer
118
Q

What types of preparations target the skin appendages (follicles, sweat glands, sebaceous glands)?

A
  • Anti-perspirants
  • Depilatories
  • Antibiotics
  • Antifungals (for bacterial and fungal folliculitis)
119
Q

What types of preparations target the systemic circulation?

A
  • Nitroglycerin patch
  • NRT patch
  • Birth control patch
120
Q

In what situations are ointments preferred?

A
  • Occulsion is required
  • Longer retention period is required
  • Avoid oleaginous bases in oozing conditions
121
Q

In which situations are creams preferred?

A
  • Whenever emollient action is required without occulusion
  • Better patient acceptance (less greasy)
122
Q

In which situations are lotions preferred?

A
  • Low viscosity and high flowability is intended
  • Where large surface are is to be treated

ex. Hairy skin areas (dandruff shampoo)

123
Q

In which situations are gels preferred?

A
  • Where API is highly soluble
  • Faster release kinetics is desirable
  • Do not use gels when skin is prone to drying or irritation, best for oily skin
124
Q

In which situations are pastes preferred?

A
  • More barrier properties are required (for oozing conditions)
  • Pastes offer longer retention times

ex. Canker sore pastes (oracort), treatment of warts when longer residence time for SA is needed

125
Q
A

PHAR 224 (6 decks)

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