Dermatologicals Flashcards
1
Q
What are main layers of the skin?
A
- Epidermis
- Dermis
- Subcutaneous tissue
2
Q
What are the layers of the epidermis?
A
Stated from outermost to innermost layer
- Stratum corneum
- Stratum lucidum
- Stratum granulosum
- Stratum spinosum
- Stratum basale
3
Q
Does the epidermis have a blood supply?
A
No
4
Q
Does the dermis have a blood supply?
A
Yes, it is also innervated. Both are important for drug delivery
5
Q
What layer of the skin attaches to the underlying muscles?
A
Subcutaneous
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)
7
Q
What are some characteristics of the stratum corneum?
A
10-15 layers of flattened aneucleated cells
Undergoes desquamation
8
Q
What are the main functions of the stratum corneum?
A
- Main permeability barrier of the skin
- Controls percutaneous absorption
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
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
11
Q
What are the main functions of the stratum lucidum?
A
- Responsible for the skin’s ability to stretch
- Contains a protein that is responsible for the degeneration of skin cells
- Lowers the effects of friction on the skin (especially in the soles and palms)
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))
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)
14
Q
What are some characteristics of the stratum spinosum?
A
Contain prickly filaments that are subject to constant pressure and friction
15
Q
What is the main function of the stratum spinosum?
A
Helps the skin resist abrasion
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
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
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
19
Q
What are the main functions of the dermis?
A
- Supports the epidermis
- Thermoregulation (vasoconstriction/dilation)
- Aid in sensation
20
Q
What is the pH of the dermis?
A
pH 7.2, closer to physiological ranges
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
22
Q
What are the functions of the subcutaneous tissue?
A
- Storing energy/insulation (due to fat deposits)
- Connects the dermis (& epidermis) to the muscles and bones
- Serves as a mechanical cushion
23
Q
What happens to the subcutaneous tissue as we age?
A
It starts to decrease in size, causing the skin above to sag
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
25
What are the advantages of subcutaneous administration vs. IM?
Subcutaneous tissue has fewer blood vessels, allowing for a more gradual rate of absorption (depot effect)
26
What happens to a topical drug once it reaches the dermis?
It can be absorbed into the systemic circulation
27
What are some frequently treated skin conditions?
1. Acne
2. Cold Sores
3. Dermatitis
4. Common warts
5. Psoriasis
6. Tinea capitis
7. Photoallergic reactions
8. Fungal skin infections
28
What are some important aspects that must be considered when developing a topical dosage form?
1. Pathophysiology of the disease condition
2. Active ingredient characteristics
3. Intended therapy (localized vs. systemic)
4. Vehicle/drug delivery system
29
What are some physicochemical criteria for a good topical dosage form?
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
30
What are some factors that affect drug bioavailability in topical dosage forms?
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
31
What are the different types of ointment bases?
1. Hydrocarbon bases
2. Absorption bases
3. Emulsifying bases
4. Water soluble bases
32
What are the different types of creams?
Oil in water (O/W) emulsions
Water in oil (W/O) emulsions
33
What is the definition of an ointment?
Contains less than 20% water and volatiles, and more than 50% of hydrocarbons, waxes, or polyethylene glycols
34
What is the definition of a cream?
An emulsion semi-solid dosage form that contains more than 20% water and volatiles, and less than 50% of hydrocarbons, waxes, or polyethylene glycols
35
What are some characteristics of ointments?
Semi-solid greasy preparations
Mostly anhydrous, but may contain dissolve or dispersed active pharmaceutical ingredient (API)
36
What are some charcteristics of creams?
Semi-solid preparations that contain both oil phase and water
37
What is the main distinction between ointments and creams?
Ointments have little amounts of water, unlike creams. Creams have a varying amounts of water
38
How can dermatological vehicles (bases) be divided into two main groups?
1. Non water-washable bases
2. Water washable vehicles
39
Which dermatological bases are non water-washable bases?
1. Oleaginous/Hydrocarbon bases
2. Absorption bases
3. Water in oil (W/O) emulsions
40
Which dermatological bases are water washable vehicles?
1. Oil in water (O/W) emulsions
2. Gels
3. Hydrophillic base
4. Emulsifying base
41
Review slide 41 for a review of dermatological bases
42
Review slide 42 for modification of dermatological bases
43
What are some properties of Oleaginous bases?
1. Hydrophobic
2. Greasy
3. Non-water washable
4. Occlusive
44
What is occlusion?
It is formation of an impermeable layer on the skin to prevent evaporation of water
45
What are the benefits of good occlusive character?
1. Increased hydration (prevent evaporation of water from skin)
2. Enhanced percutaneous absorption due to increased retention on skin
46
Are oleaginous bases preferred for widespread use on the skin?
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
47
What are some advantages of oleaginous bases?
1. Very stable vehicles
2. Non-irritating
3. Non-sensitizing
4. High compatibility with drugs
48
What are some the disadvantages of oleaginous bases?
1. Greasiness
2. Stain clothing
3. Difficult to remove
4. Low patient acceptance (emulsion bases are more preferred)
49
What are some common ingredients of oleaginous bases?
1. Fats and fixed oils
2. Penetration enhancers
3. Levigating agent
4. Antimicrobial preservatives (not commonly used in extemporaneous compounding)
50
What is the mechanism of action of penetration enhancers?
Fluidization of stratum corneum lipids. This increases the permeability and absorption of drug into skin
51
What is the purpose of a levigating agent?
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
What are the two compounding methods for topical dosage forms?
1. Fusion (melt)
2. Incorporation
53
What is the process for fusion compounding methods for topical dosage forms?
1. Components are melted together
2. Cooled with constant stirring until congealed
54
When using the fusion compounding method, should the temperature be set to the lowest or highest melting points?
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
What is the process for incorporation compunding method for topical dosage forms?
Mix one semi-solid formulation into another via geometric dilution
1. In a mortar with pestle
2. On a slab with spatula
56
Can fusion and incorporation compunding methods be combined?
Yes
Order of steps:
1. Fusion
2. Incorporation
57
What are some relevant beyond-use-dates (BUDs) for extemporaneously compounded topical dosage forms?
1. Non-preserved aqueous: 14 days
2. Preserved aqueous: 35 days
3. Nonaqueous dosage forms: 90 days
58
How are absorption bases formed?
Adding a W/O emulsifier to an oleaginous base
59
What are some characteristics of absorption bases?
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
What are some distinct applications of absorption bases?
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
What are the main components of absorption bases?
Very similar to oleaginous bases (fats, mineral oil, petrolatum, waxes), but also include w/o emulsifying agent
62
What are the two main types of absorption bases?
Type 1 (Anhydrous bases)
Type 2 (Lanolin)
63
What are some qualities of a Type 1 absorption base?
Type 1 absorption bases are used for specialty compunding for drugs like HRT
ex. Cholesterol
64
What are some qualities of a Type 2 absorption base?
Type 2 (Lanolin) can take up to two times its weight of water
Acts as W/O emulsifier
65
What are some additional additives for absorption bases?
1. Antioxidants
2. Penetration enhancers
66
What are some desired characteristics for antioxidants in absorption bases?
1. Effective at low concentrations
2. Soluble in vehicle
3. Compatible with pharmaceutical excipients and wide range of drugs
4. Odourless, tasteless
67
What are some examples of perservatives used in absorption bases?
Extemporaneously Compounded:
butylated hydroxy toluene (BHT) and butylated hydroxy anisole (BHA)
Commercial preparations:
alpha-tocopherol
68
Can hydrophillic levigating agents be used in absorption bases?
Yes, both hydrophobic and hydrophillic levigating agents can be also be used in absorption bases
69
What are qualities of emulsifying bases?
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
What are the components of emulsfying bases?
Very similar to oleaginous bases (fats, mineral oil, petrolatum, waxes), but also contain o/w emulsifiers and other surfactants
71
What is the common compounding method for emulsifying agents?
Fusion method is more commonly applied
72
What types of levigating agents are used in emulsfying bases?
Both hydrophillic and hydrophobic agents can be used
Emulsfying bases themselves can be used as a levigating agent in most final formulations
73
What are the two types of creams?
W/O emulsion
O/W emulsion
74
What are some qualities of w/o emulsions?
1. Greasier than O/W emulsions
2. Non-water washable
3. Emollient
4. Capable of absorbing oil-soluble compunds from the skin
75
What are some qualities of o/w emulsions?
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
What are some common additives for emulsions?
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
What are the most common preservatives used in emulsions?
Parabens (use is growing)
78
Are humectants found in high concentrations in emulsions?
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
What are the main methods of compounding a cream base?
1. Fusion
2. Incorporation
80
How is the fusion method used to form cream bases?
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
How is the incorporation method used to form cream bases?
Commonly performed with commercial bases
Mix one semi-solid formulation into another (usually on glass plate)
82
Need to add lotion flashcards
83
What is the definition of a paste in a pharmacology sense?
An oleaginous that contains 20% or more solids suspended in the base
84
What are some qualities of a paste?
Very stiff consistency
Form a thick impermeable layer on the skin
ex. Oracort
85
Should pharmacists use mortar and pestle to levigate pastes?
No, use glass slab for incorporation
86
What are some properties of hydrophillic bases?
1. They contain water-washable components
2. Non-oclussive
3. Non-irritant
4. Cannot take up more than 8% water
87
What are some incompatible ingredients seen in hydrophillic bases?
1. Phenols, iodine, KI, tannic acid, silver
2. Reduce the antimicrobial actvity of quartenary compounds and parabens
3. Inactviate bacitracin, pencillin
88
What are the advantages of hydrophillic bases?
1. Anhydrous (useful for drugs that hydrolyze
2. Good patient compliance (non-staining and non-occlusive)
89
What are some qualities of gels?
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
Can gels be used on dry skin?
No, it has poor moisture barrier
91
How are gels compounded (Carbomer)?
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
What is percutaneous absorption?
It is the amount of drug that passes from the vehicle into the stratum corneum of the skin
93
How does the skin act as a passive barrier for topical drug absorption?
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
What are the routes of percutaneous absorption?
1. Across stratum corneum
2. Via appendages
95
What are the two routes for percutaneous absorption across the strateum corneum?
Intracellular route (pass through multiple cells)
Intercellular route (drug passes around skin cells through the stratum corneum)
96
How is drug percutaneously absorbed via appendages?
Negligible process, but more pronounced for microbial actvity
Drug enters through sweat ducts, sebaceius glands, and hair follicles
97
What are some factors that affect percutaneous absorption?
1. Drug factors
2. Vehicle factors
3. Skin factors
98
How do drug factors affect percutaneous absorption?
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
How do vehicle factors affect percutaneous absorption?
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
Do corticosteroid ointments have lower potency vs. corticosteroid creams?
No, corticosteroid ointments have higher potency vs. creams of the same active ingredient
Difference is due to increased occulsive factor of ointments
101
What skin factors affect percutaneous absorption?
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
What are the most accurate animal models for studying percutaneous absorption?
1. Pigs (closest to human)
2. Guinea pigs
3. Hairless mouse
103
What is the blanching test?
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
What does Fick's Law describe?
Fick's Law relates the rate diffusion of a substance across a membrane to be proportional with concentration gradient
Review slide 133
105
What is the equation of Fick's Law?
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
Why is drug concentration elevated at the skin's surface?
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
Why does drug concentration rapidly fall when leaving the skin and entering the receptor compartment?
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
What is the utility of Fick's Law?
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
What is the diffusion coefficient of the drug?
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
What is partition coefficient?
Ratio of drug concentration in Phase A (vehicle) to the concentration in Phase B (stratum corneum)
111
What is the permeability coefficient?
A measure of the rate at which a molecule can cross a membrane
112
What is the equation for permeability coefficient?
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
Is a smaller partition coefficient responsible for better penetration?
False
Greater partition coefficient = more drug into skin = better penetration
114
What is the main difference between dermal and transdermal formulations?
They are both topical dosage forms, but drug in transdermal formulation is intended to pass through the skin and enter the systemic circulation
115
What are the target regions for topical formulations?
1. Skin surface and stratum corneum
2. Viable epidermis and dermis
3. Skin Appendages
4. Systemic Treatment
116
What types of preparations target the **stratum corneum**?
- Emollients and moisturizers
- Protective films (ex. sunscreen)
- Topical Antibiotics
- Keratolytics
117
What types of preparations target the **epidermis and dermis**?
- Topical NSAIDs
- Local anesthetics
- Anti-histamines
- Anti-cancer
118
What types of preparations target the **skin appendages** (follicles, sweat glands, sebaceous glands)?
- Anti-perspirants
- Depilatories
- Antibiotics
- Antifungals (for bacterial and fungal folliculitis)
119
What types of preparations target the **systemic circulation**?
- Nitroglycerin patch
- NRT patch
- Birth control patch
120
In what situations are ointments preferred?
- Occulsion is required
- Longer retention period is required
- Avoid oleaginous bases in oozing conditions
121
In which situations are creams preferred?
- Whenever emollient action is required without occulusion
- Better patient acceptance (less greasy)
122
In which situations are lotions preferred?
- Low viscosity and high flowability is intended
- Where large surface are is to be treated
ex. Hairy skin areas (dandruff shampoo)
123
In which situations are gels preferred?
- 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
In which situations are **pastes** preferred?
- 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
