Dermatologics Flashcards

1
Q

Layers of the Epidermis (from Superficial to Deep)?

A

“Carter Licks Gooch & Sweaty Balls”

1) Stratum Corneum

2) Stratum Lucidum

3) Stratum Granulosum

4) Stratum Spinosum

5) Stratum Basale

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2
Q

pH of Epidermis?

A

5.5

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3
Q

The Epidermis is comprised of what cell types?

A

1) Keratinocytes (synthesize Keratin)

2) Melanocytes (synthesize Melanin pigment)

3) Dendritic / Langerhans Cells (immune cells that determine adaptive immune response post-pathogenic exposure)

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4
Q

Stratum Corneum other name?

A

Carter 24/7 :)
Horny Layer

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5
Q

Stratum Lucidum other name?

A

Clear Layer

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6
Q

Stratum Granulosum other name?

A

Granular Layer

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7
Q

Stratum Spinosum other name?

A

Prickle Cell Layer

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8
Q

Stratum Germinativum / Basale other name?

A

Basal Layer

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9
Q

Major role of Stratum Corneum?

A

-Permeability Barrier
-Ctrl of Percutaneous Absorption

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10
Q

The Stratum Corneum also undergoes a phenomenon known as “Desquamation”. Describe this process.

A

-Cells from top outermost layer of skin are removed.

-This process enables skin to continuously create uniform “brick & mortar” structures. Also creates a barrier that enables the skin to rehydrate & resist assault from pathogens.

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11
Q

T or F: Cells of the Stratum Lucidum layer are nucleated.

A

False… Are anucleated.

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12
Q

What role does the Stratum Lucidum play?

A

-Skin stretchability.

-Contains protein that degenerates skin cells.

-Lowers skin friction (espec. in soles of feet & hands).

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13
Q

Topical prodrug activation takes place first at what Epidermal layer?

A

Stratum Granulosum

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14
Q

Role of Stratum Granulosum?

A

-Bioreactor Site (duh Prodrug last card stupidddd).

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15
Q

Role of Stratum Spinosum?

A

-Filament Bundles are subject to constant pressure & friction; thus, this layer helps the skin resist abrasion.

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16
Q

T or F: Cells of Stratum Germinativum are nucleated.

A

True!

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17
Q

T or F: The Stratum Germinativum layer consists of multi-layered cuboidal / columnar cells.

A

False… Is a singular layer.

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18
Q

What is the normal turnover time of cells contained within the Basal (ie. S. Germinativum) Layer?

A

28d = Normal… 4d in Psoriatic patients.

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19
Q

Given that cells of the Basal Layer are nucleated, what important role do they play as it pertains to the overall functioning of the Epidermis?

A

-Because they are capable of dividing via Mitosis, provide Germinal Cells necessary in order to regenerate Epidermal sublayers.

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20
Q

The Dermis is comprised of ___% Collagen & ___% Elastin.

A

75%; 4%

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21
Q

What cell types are contained within the Dermis?

A

Fibroblasts, Mast Cells, Histiocytes

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22
Q

T or F: The Dermis is supplemented with rich Neurological & Vascular supplies.

A

True.

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23
Q

What are the three primary roles of the Dermis?

A

-Structural Support
-Thermoregulation
-Sensation

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24
Q

Average pH of the Dermis?

A

7.2

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25
Q

Role of the Hypodermis & Subcutis (ie. Subcutaneous Tissue)?

A

-Energy Storage

-Connect Dermis to Muscles & Bones

-Insulation / Cushioning

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26
Q

Why does our skin tend to sag as we age?

A

Shrinking Hypodermis

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27
Q

The Stratum Corneum requires ___-___% water to maintain its bendability (otherwise it chaps, cracks & splits).

A

10-20%

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28
Q

Sebaceous & Eccrine Sweat Glands contribute secretions to the Acid Mantle, which provides the skin with protective abilities. What is the pH of this Acid Mantle?

A

4.2 - 5.6

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29
Q

How many times less permeable is the Stratum Corneum (vs. other bodily membranes)?

A

10 000x less

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30
Q

Is the amount of drug penetrance through the “Shunt Route” (ie. Hair Follicles & Glands) important to take note of?

A

-Negligible… Follicles & Glands contribute 0.1% of total skin surface area.

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31
Q

UVB radiation induces burning of the skin. At what wavelength range does this occur?

A

290 - 320nm

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32
Q

UVA radiation is less damaging to the skin, but still contributes to aging & pigmentation processes. At what wavelength range does this occur?

A

320 - 400nm

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33
Q

How does the skin respond to UV radiation?

A

-Erythema
-Pigmentation
-Epidermal Thickening
-Chronic Rxn’s
-Aging
-Pre Maligancies
-Malignancies

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34
Q

What is the major rate-limiting barrier to transdermal drug delivery?

A

Stratum Corneum

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35
Q

Provide an example of a condition that impacts the barrier function of the Epidermis.

A

Atopic Dermatitis

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36
Q

What important Physicochemical properties must Dermatological formulations possess?

A

-Active Ingredient / Adjuvant Stability

-Uniform particle size & distribution within the Dispersed Phase

-Prevention of water loss / volatile compound formation

-Homogeneity

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37
Q

What factors affect vehicle selection in terms of optimizing bioavailability?

A

-Skin Disease / Condition

-Drug Release Rate from Vehicle

-Percutaneous Absorption Promotion

-Occlusion Requirement

-Drug Stability in Ointment Base

-Drug influence on base consistency

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38
Q

Ointments are comprised of </= ___% H2O & Volatiles, and >/= ___% Hydrocarbons, Waxes, or PEGs as the vehicle for external skin application.

A

</= 20% Water

> /= 50% HCs, Waxes, PEGs

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39
Q

Creams are comprised of >___% H2O & Volatiles, and <___% Hydrocarbons, Waxes, or PEGs as the vehicle for external skin application.

A

> 20% Water

< 50% HCs, Waxes, PEGs

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40
Q

Pastes are semisolid dosage forms that contain large proportions (ie. ____ - ____%) of solids, finely dispersed in a fatty vehicle for external skin application.

A

20 - 50% solids

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41
Q

What is the role of a Gelling Agent?

A

Provide Solution Stiffness &/or Colloidal Dispersion

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42
Q

What are the classes of Derm Vehicles?

A

Hydrocarbon Bases
Absorption Bases
Emulsifying Bases
Water Soluble Bases

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43
Q

Ointments differ from Creams how (regarding water / oil composition)?

A

Ointment: Mostly anhydrous (may contain dissolved or dispersed API).

Cream: Contains both oil & water.

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44
Q

Non Water Washable Bases include what?

A

Oleaginous / HC Bases
Absorption Bases
W/O Emulsion Bases

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45
Q

Water Washable Vehicles include what?

A

O/W Emulsion Bases
Gel Bases
Hydrophilic Bases
Emulsifying Bases

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46
Q

What are some examples of Hydrocarbon / Oleaginous Bases?

A

Petrolatum
Wax
Synthetic Esters

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47
Q

What are some examples of Absorption Bases?

A

Anhydrous: Hydrophilic Petrolatum, Anhydrous Lanolin

W/O Emulsion: Lanolin, Cold Cream

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48
Q

Examples of Emulsion Bases?

A

Hydrophilic Ointment
Vanishing Cream

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49
Q

Examples of Water Soluble Bases?

A

PEG 400 + 4000 (40 : 60 ratio)

Propylene Glycol + Ethanol + 2% w/w HPC

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50
Q

The addition of a W/O Emulsifier transforms an Oleaginous Base into what (Slide 44 Diagram)?

A

Absorption Base

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51
Q

The addition of an O/W Emulsifier transforms an Oleaginous Base into what (Slide 44 Diagram)?

A

Emulsifying Base

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52
Q

Major property of Hydrocarbon / Oleaginous Bases?

A

HIGHLY OCCLUSIVE (increase skin hydration by preventing water evaporation)

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53
Q

Issues with Hydrocarbon / Oleaginous Bases?

A

-Greasy (contributes to low patient compliance)

-Staining

-Hard to remove from skin

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54
Q

Main ingredients of Oleaginous Bases are what?

A

1) Fats / Fixed Oils & Mineral Oil

2) Petrolatum / White Petrolatum

3) Waxes

4) Paraffin

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55
Q

What is the big issue with Fats / Fixed Oils being used in Oleaginous Bases?

A

Rancidity (upon air / light / high temp exposure)

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56
Q

Primary roles of Petrolatum / White Petrolatum in Oleaginous Bases?

A

-Act as an Emollient (ie. Skin Softener).

-Occlusive (moisturizes skin by preventing water evaporation).

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57
Q

What are the other names for White Petrolatum?

A

White Soft Paraffin
White Petroleum Jelly
Vaseline

58
Q

What is the role of Waxes in Oleaginous Bases?

A

-Stiffening Agent & Emollient Properties.

59
Q

Examples of Waxes used in Oleaginous Bases?

A

Spermaceti Wax
Cetyl Esters Wax
White Wax

60
Q

Role of Paraffin in Oleaginous Bases?

A

-Provides stability & non-reactivity to the formulation.

61
Q

What are some examples of
Additives within Oleaginous Bases?

A

1) Penetration Enhancers

2) Levigating Agent

3) Antimicrobial Preservatives (but only in commercial products)

62
Q

What are desirable Penetration Enhancer properties?

A

-Not toxic, irritating, or allergenic

-No causing fluid / electrolyte / material loss

-Immediate / predictable effects & ability to restore skin’s barrier properties after penetrance

-Odorless / tasteless / colorless / cheap / nice spreadable feel

63
Q

How do Penetration Enhancers work?

A

Fluidizes lipids of the Stratum Corneum

64
Q

Examples of Penetration Enhancers?

A

Isopropyl Myristate
Oleic Acid
Oleyl Alcohol

65
Q

Role of Levigating Agents?

A

-Aid in incorporation / particle size reduction of a powder into ointments.

66
Q

Levigating do not exceed what percentage of the final formulation?

A

5%

67
Q

Example of Levigating Agent?

A

Mineral Oil

68
Q

T or F: The Fusion compounding method is more commonly employed by using increasing melting points.

A

False… Decreasing order of melting points (ie. Highest MP substance to Lowest MP) more common.

69
Q

What advantage does performing Fusion compounding with increasing melting points have?

A

-Components can incorporate into molten ingredients w/o having to reach their MP…

-Limit high heat exposure for our APIs, more rigorous temp control.

70
Q

Provide some examples of liquid APIs / Excipients that require Levigating Agents (Slide 56).

A

Coal Tar: Polysorbate 80

Peruvian Balsam: Castor Oil

Ichtammol: Glycerin / Fixed Oils

71
Q

Water Containing Oral Formulations have a BUD of how many days?

A

14d

72
Q

Water Containing Topical / Dermal & Mucosal Liquids / Semisolids have a BUD of how many days?

A

30d

73
Q

Non-Preserved Aqueous formulations have a BUD of how many days? Preserved Aqueous formulations?

A

NPA: 14d
PA: 35d

74
Q

Non-Aqueous Dosage Forms have a BUD of how many days?

A

90d

75
Q

Compounded Ointments have a BUD of how many days at room temp?

A

28d

76
Q

What type of Emulsifier (O/W or W/O) does an Absorption Base contain?

A

W/O (allows for water absorption & formation or expanded W/O emulsions)

77
Q

Type I Anhydrous Bases include what? Type II?

A

I: Glyceryl Monostearate, Glyceryl Monooleate, Cholesterol

II: Lanolin

78
Q

What specialty compounding situation would we see Type I Anhydrous Bases used in?

A

Hormone Replacement Therapy (HRT) Compounds

79
Q

Other additives for Absorption Bases?

A

1) Antioxidants (ie. BHA, BHT, Alpha-Tocopherol).

2) Penetration Enhancers (same as Oleaginous Bases… ie. Isopropyl Myristate, Oleic Acid, Oleyl Alcohol).

80
Q

Ideal Antioxidant properties?

A

-Stable & Soluble in Vehicle

-Effective at [Low]

-Excipient & Drug Compatibility

-Odorless & Tasteless

81
Q

What is unique about the potential Levigating Agents that can be used for Absorption Bases (in comparison to Oleaginous Bases)?

A

Hydrophilic Levigating Agents can be used (ie. Glycerol, Propyleneglycol).

82
Q

When compounding Salicylic Acid, what must be done in order to avoid potential safety concerns?

A

Utilize Glove Box (burnsssssss).

83
Q

Emulsifying Bases contain what type of Emulsifying Agent (O/W or W/O)?

A

O/W

84
Q

What additional components comprise Emulsifying Bases?

A

O/W Emulsifiers (largely Surfactants)

85
Q

Would it be appropriate to compound an Emulsifying Ointment BP Base with Cationic Compounds?

A

False… Incompatible. It’s actually compatible with Anionic Compounds.

86
Q

What type of compounds are compatible with Cetrimide (ie. Form of Emulsifying Base)?

A

Cationic

87
Q

Cetomacrogol (ie. Emulsifying Base Form) is compatible with what types of compounds? Incompatible with what?

A

Compatible: Non-Ionic Compounds

Incompatible: Phenols

88
Q

Which compounding method is more commonly employed for Emulsifying Bases?

A

Fusion Method&raquo_space;> Incorporation Method

89
Q

What example in class was covered where we formed an In-Situ Emulsifying Agent?

A

Sodium Borate… Combination with FFA’s present in the Waxes of a Cold Cream generated Na+ Salts (ie. Soaps) that acted as an Emulsifier.

90
Q

As water is added to O/W Emulsions, what additional excipients are required?

A

1) Anti-Microbials (to stunt growth)

2) Humectants (keeps water in formulation & increases shelf life)

91
Q

Examples of Anti-Microbial Preservatives?

A

BIG ONES (!!!): P-Hydroxybenzoates (ie. Methyl-, Propyl-, Butylparabens).

Others:
-Imidazolidinyl Urea (on the decline)
-Alcohols
-Acids
-Mercurials
-Phenols

92
Q

Examples of Humectants?

A

PEG
Glycerol
Propylene Glycol

93
Q

Lab Scenario:

When compounding Cream Bases, why is the Water Phase in Fusion Compounding heated 5 degrees higher than Oil Phase?

A

-To prevent premature solidification of the Oil Phase.

94
Q

Example in class we covered where two medicated creams could be compounded together via Incorporation within the Ointment Jar itself?

A

Benzaclin Kits… AB mixed into the cream upon dispensing (& all done within the Ointment Jar itself).

95
Q

Pastes are comprised of ___% (or more) solids suspended in base.

A

20%

96
Q

What are the most commonly used agents for Pastes?

A

Pet & White Pet

97
Q

What therapeutic effects do the very stiff consistency & thickness of Non-Water Washable Pastes have?

A

-Localization of materials to defined skin areas

-Form impermeable layers on the skin (serving protective measures)

98
Q

Examples of Pastes used in practice?

A

Oracort
Zinc Oxide
Lassar’s Paste

99
Q

What is the compounding method of choice for Pastes?

A

-Incorporation on glass slab (as formulation is very thick & requires larger SA for mixing).

100
Q

T or F: It’s impractical to use levigating agents when preparing pastes.

A

True

101
Q

What compounds are incompatible with Hydrophilic Bases?

A

Phenols
Iodine
KI
Tannic Acid
Silver
Mercury
Bismuth Salts

102
Q

What’s the big deal about the incompatible compounds with Hydrophilic Bases?

A

1) Decrease Anti-Microbial Activity of Quaternary Ammonium Cpd’s & Parabens

2) Inactivate certain ABs (Bacitracin, Penicillin)

103
Q

Do we need Antimicrobials & Humectants in Hydrophilic Bases?

A

NOOOOO (they are Water Soluble, but the Bases themselves are Anhydrous).

104
Q

What types of Water-Soluble Antioxidants are used in Hydrophilic Bases?

A

Ascorbic Acid
Sodium Bisulfite

105
Q

What’s the primary compounding method for Hydrophilic Bases?

A

Fusion (lowest to highest MP)… PEG ingredients should be liquidated for mixing.

-Glass Beaker
-Porcelain Dish
-Stainless Steel Mortar or Steam Jacketed Vessel

106
Q

What skin types are Gels best used for?

A

Oily Skin (weak moisture barrier, so poor for dry skin)

107
Q

Nice feature of Gels as it pertains to Water-Soluble Drugs?

A

Easily incorporated either dissolved in aqueous phase or dispersed in Gel.

108
Q

Unique feature of Emugels?

A

1) Emulsion incorporation into the gel creates suitable dosage form for Hydrophobic Drugs too.

109
Q

Natural Gums used as Gelling Agents within Gel preps?

A

Tragacanth
Agar
Pectin
Alginates

110
Q

Issue with natural gums in gel preps?

A

1) Hazy appearance (aesthetically less pleasing)

2) Very sticky

3) Microbe contamination

111
Q

Examples of Semi-Synthetic / Synthetic Polymers used as Gelling Agents within Gel Preps?

A

Methylcellulose
H.methycellulose
H.propylcellulose
Carbopol
Clays

112
Q

Most common skin conditions in which gels are typically used?

A

Acne (due to often oily nature of skin)

113
Q

Describe the process of preparing a Carbomer 934 Gel.

A

1) Water-Soluble Ingredients dissolve in H2O (in beaker).

2) Carbomer sprinkling on surface… Stir vigorously.

3) NaOH, KOH, Triethanolamine addition so pH = 6-7 (until clear gel forms).

4) Qs with H2O if needed.

114
Q

Describe the process of preparing a Carboxymethylcellulose Gel.

A

1) Water-Soluble Ingredients in 1/2 H2O (Beaker #1).

2) Heat Beaker #2 (other 1/2 of H2O) to 70-80 Celsius.

3) Sprinkle Carboxymethylcellulose into hot water beaker (forms slurry). Stir it vigorously like Carter beats his meat.

4) Hot goes into Cold Beaker… Stir vigorously until cools to room temp.

5) Qs H2O PRN… Refrigerate after overnight for full hydration.

115
Q

Define Percutaneous Absorption & quantify it.

A

-Is simply absorption of drug through the skin… Amount of drug passing from vehicle into the Stratum Corneum.

116
Q

Rate limiting step of passive drug diffusion through skin?

A

Drug Diffusion through Stratum Corneum (did you even read last card you stoooooopid).

117
Q

Drug Factors influencing Percutaneous Absorption?

A

1) Drug Concentration in Prep… Provides high concentration gradient across skin.

2) Partition Coefficient (P)… Measure of drug lipophilicity & an indication of ability to cross lipid barrier.

3) Drug / Skin Binding.

118
Q

Vehicle Factors influencing Percutaneous Absorption?

A

1) pH (determines degree of ionization).

2) Co-Solvents (define drug concentrations on skin).

3) Drug Release from Vehicle (optimized with appropriate vehicle selection).

4) Penetration Enhancers (temp. increase in skin permeability).

119
Q

Skin Factors influencing Percutaneous Absorption?

A

1) Skin Age (kid vs. adult vs. old).

2) Condition of Skin.

3) Localized Stratum Corneum thickness.

4) Skin Metabolism.

5) Circulation Effects.

6) Inter-Special Differences (vet use different than human).

120
Q

Which animal model best mimics In-Vivo Percutaneous Absorption in humans?

A

Pigs

121
Q

Other Animal Models used for In-Vivo analysis of a drug’s Percutaneous Absorption?

A

Guinea Pigs
Monkeys
Hairless Mice
Rabbits

122
Q

Why are Rats, Rabbits, Guinea Pigs less suitable for estimating Percutaneous Absorption rates in humans In-Vivo?

A

-Tendency to overestimate human skin absorption & drug penetration through the skin.

123
Q

Describe the Blanching Test. What is it assessing?

A

-Qualitative assessment of Topical Corticosteroid availability / potency…

-Uses skin whitening to estimate rate & extent of steroid diffusion (with whitening intensity directly correlated to topical drug availability).

124
Q

Describe the process of Fick’s Law as it pertains to passive drug diffusion through the skin.

A

-Drug API in Vehicle encounters Stratum Corneum… Drug accumulates at the interface (C1), causing concentrations at the interface to increase.

-Then, Sink Effect (C2) occurs… Drug concentration drops drastically at the interface, as it desires to diffuse across the Stratum Corneum into the Receptor Compartment.

125
Q

True or false diffusion past the corneum is a constant value.

A

False- tis always changing

126
Q

If we increase SA how does rate change (Fick’s law)

A

increases

127
Q

If skin gets thicker how does fick’s law change?

A

decreases

128
Q

What does a large partition coefficient tell us?

A

PENETRATE ME MORE- Adam to Carter
more effective

129
Q

When would we want to target corneum layer?

A

to hydrate skin
topical infections
barrier
exfolients

130
Q

What does viable epidermis mean?

A

part of epidermis that has metabolic activity

131
Q

When would we want to target the viable epidermis and dermis?

A

steroids,anesthetic, antihistamines

132
Q

Where do skin appendages reside?

A

dermis layer

133
Q

When would we want to target skin appendages?

A

for antiperspirant
infection folliculitis
fungal folliculitis

134
Q

When would we prefer lotions?

A

for hairy areas
and large surface area

135
Q

When would we want pastes?

A

for long contact time
ie) warts,

136
Q

Sigh*** What is side effect of topical steroids

A

skin thinning, redness, spider veins

137
Q

If we add a fluorine onto C9 of CS what happens?

A

more antiinflamm

138
Q

If we add substituents onto C17 or C21 on CS what happens?

A

more lipophilic= more penetrate

139
Q

If we add a alpha-alkoxyarbonyl on C16 of CS what happens?

A

Lower systemic s/e

140
Q

What penetration enhancers for CS do we use?

A

terpene
pyrrolidone

141
Q
A