Dermatologicals Flashcards
What are the advantages and limitations of dermatological preparations?
advantages:
-applied directly to site of action
-avoids systemic side effects
-allows combinatorial treatment strategies
-lower dosages
disadvantages
-slow onset leading to longer treatment
-dependence of PC as topical formulation has to overcome the protective barrier of the skin at therapeutically effective concentrations
-may encounter disease specific limitations
What is the largest organ in the body?
the skin
-surface area: 2m squared (70kg)
What are the three layers of the skin?
epidermis
dermis
subcutaneous tissue
Describe the epidermis.
average thickness varies depending on part of the body (avg ~200um)
contains several cell layers
pH 5.5
composed mainly of keratinocytes which synthesize keratin, melanocytes and dendritic cells (immune cells)
What are the 5 layers of the epidermis?
stratum corneum (horny layer)
stratum lucidum (clear layer)
stratum granulosum (granular layer)
stratum spinosum (prickle cell layer)
stratum germinativum/basale (basal layer)
Describe the stratum corneum.
10-15 layers of flattened keratinized anucleated dead cells
average thickness: 10um
undergoes desquamation
What is the role of the stratum corneum?
major permeability barrier of the skin
controls percutaneous absorption
What is desquamation and why is it important?
skins way of recovering or healing from some type of damage
-cells from top outer layer are removed
-skin is optimally healthy when it has a normal rate of desquamation
-creates a barrier which enables skin to retain hydration and resist assault
Describe the stratum lucidum.
thin layer of translucent, extremely flattened cells, only visible in the thickest skin
anucleated cells
cytoplasm filled with filaments
What is the role of the stratum lucidum?
capability of the skin to stretch
contains a protein that is responsible for the degeneration of skin cells
lowers the effects of friction in skin
Describe the stratum granulosum.
1-5 layers of flattened, many-sided cells
keratinocytes contain keratohyalin granules which discharge a cement-like substance that bind cells together (barrier against foreign material)
What is the role of the stratum granulosum?
site of biochemical activity (bioreactor)
Describe the stratum spinosum.
cuboidal, many sided or flattened keratinocytes
keratinocytes contained filaments
subject to constant pressure and friction
What is the role of the stratum spinosum?
helps the skin resist abrasion
Describe the stratum germinativum.
cells held together by desmosomes
single layer of cuboidal or columnar cells
nucleated basal cells (undergo mitosis)
turnover time is 28 days (4 days in psoriasis)
What is the role of the stratum germinativum?
provides the germinal cells necessary for the regeneration of the layers of the epidermis
What is the composition of the dermis?
matrix of connective tissue
cells
vascular supply
neural supply
skin appendages (glands and follicles)
Describe the dermis.
thickness 3-5um
presence of nerves and blood vessels (provide O2 and nourishment)
pH 7.2
What is the role of the dermis?
support
thermoregulation
aid in sensation
What is the composition of the subcutaneous tissue?
fibrofatty layers
also houses immune cells like macrophages
What is the role of the subcutaneous tissue?
storing energy
connecting dermis to muscle and bone
insulating body
mechanical cushion
What happens to the hypodermis as you age?
hypodermis decreases in size and your skin starts to sag
What are the mechanical and protective functions of the skin?
mechanical:
-elasticity (can stretch 1.5x)
-maintain suppleness (stratum corneum must have 10-20% water)
protective:
-microbiological barrier (bacterio/fungistatic)
-chemical barrier (traffics cpds)
-radiation barrier
-heat regulator
How do eccrine glands provide cooling?
water evaporation of sweat
What are the important aspects to target dermatological drug delivery?
pathophysiology of disease
active ingredient characteristics
intended therapy (localized v systemic)
vehicle/drug delivery system
What is the physicochemical criteria for dermatological formulations?
stability of active ingredient
stability of adjuvants
rheological properties
prevention of water loss or volatile cpds
phase changes
particle size, particle distribution of dispersed phase
apparent pH
What is the cosmetic criteria for dermatological formulations?
pharmaceutical elegance
easy transfer from container
spreads readily and smoothly
leaves no residue or stain
adheres to treated area without being tacky or difficult to remove
What are the factors that influence selection of vehicle for optimum bioavailability?
skin disease or condition
rate of the release of drug from vehicle
promotion of percutaneous absorption
requirement for occlusion
short and long term stability of drug in base
influence of drug on consistency of base
What are the four possible bases for ointments?
hydrocarbon bases
absorption bases
emulsifying bases
water soluble bases
What is the definition of an ointment?
contains <20% water and volatiles and >50% of hydrocarbons, waxes, or PEGs as the vehicle for external application to the skin
What is the definition of a cream?
an emulsion semisolid dosage form that contains >20% water and volatiles and <50% of hydrocarbons, waxes, or PEGs as the vehicle for external application to the skin
What is the definition of a paste?
a semisolid dosage form that contains a large proportion (20-50%) of solids finely dispersed in a fatty vehicle for external application to the skin
What is the definition of a gel?
a semisolid dosage form that contains a gelling agent to provide stiffness to a solution or colloidal dispersion for external application to the skin
-may contain suspended particles
Ointments are _____ preparations and mostly ____, but may contain dispersed or dissolved API.
semisolid greasy preparation’
anhydrous
Creams are _____ preparations that contain both ___ phase and ____.
semisolid preparations
oil phase and water
True or false: ointments and creams can be differentiated based on the viscosity of the formulation rather than the formulation
false
What are examples of non water washable bases?
oleaginous/hydrocarbon bases
absorption bases
W/O emulsion bases
What are examples of water washable vehicles?
O/W emulsions
gels
hydrophilic bases
emulsifying bases
What is the other name for oleaginous bases?
hydrocarbon bases
Describe oleaginous bases.
hydrophobic
greasy
non-water washable
occlusive:
-increased hydration
-enhanced percutaneous absorption due to increased retention on skin
emollient (soften skins)
What is occlusion?
formation of an impermeable layer on the skin to prevent evaporation of water
What are advantages and disadvantages of oleaginous bases?
advantages:
-very stable vehicles
-non irritating
-non sensitizing
-high compatibility with drugs
disadvantages:
-greasiness
-stain clothing
-difficult to remove
-low patient acceptance
What are the main ingredients of oleaginous bases?
liquids:
-fats and fixed oils (can become rancid)
-mineral oil
semisolids
-petrolatum (emollient, occlusive)
solids:
-waxes (stiffening agent, emollient properties)
-paraffin (stable, non-reactive)
What are the additives for oleaginous bases?
penetration enhancers
levigating agents
What are the properties of ideal penetration enhancers?
non-toxic, non-irritating, non-allergenic
immediate and predictable effect and immediate recovery of the barrier property of the skin after removal
doesnt cause loss of body fluids/electrolytes
compatible with drugs and excipients
good drug solvent
cosmetically acceptable
odourless, tasteless, colourless, and inexpensive
What is the mechanism of penetration enhancers?
fluidization of stratum corneum lipids
What are examples of penetration enhancers?
isopropyl myristate
oleic acid
oleyl alcohol
What is the use of a levigating agent?
liquid used as an intervening agent to aid the incorporation and particle size reduction of a powder into an ointment
How much of the final weight of a formulation can a levigating agent take up?
maximum 5% of final formulation
What is an example of a levigating agent used in oleaginous bases?
mineral oil
Do we need preservatives for oleaginous bases?
no
-theres no water in the formulation
Describe fusion as a compounding method for oleaginous bases.
components are:
1. melted together
2. cooled with constant stirring until congealed
tools: glass beaker, porcelain dish, stainless steel mortar, hot plate, jacketed vessel
True or false: when using fusion as a compounding method for oleaginous bases you must start heating in reverse order (starting with highest melting point)
false
you can start with either lowest or highest melting point
Describe incorporation as a compounding method for oleaginous bases.
mixing of one semisolid formulation into another
-in a mortar with pestle
-on a slab with spatula
geometric dilution
Describe incorporation of solid APIs or excipients as a compounding method for oleaginous bases.
in a mortar with pestle or on a slab with spatula
geometric dilution or use a levigating agent
API can be dissolved in an oil
What are the two possible packaging options for extemporaneous compounding of dermatologicals?
ointment jar
Topi-Click for HRTs
What is a suggested AUX label to have on extemporaneously compounded dermatological?
for external use only
What are the options for a BUD of ointments?
nonaqueous=90 days (USP)
28 days (Medisca)
either is fine, 28 days is just more conservative
Describe absorption bases.
non-water washable bases
-hydrophobic
-greasy
-anhydrous; hydrophilic components provide water-absorbing properties
-upon water addition form W/O emulsions
-occlusive
-emollient
contain an oleaginous material and a W/O emulsifier so that they can absorb water or expand W/O emulsions
What is an example of a condition where absorption bases are used and why?
oozing conditions
they are not easily removed with water
What are the main components of absorption bases?
similar to oleaginous bases:
-fats and fixed oils
-mineral oil
-petrolatum
-waxes
other addition is the emulsifier helping in inducing a water absorbing capacity
What are examples of anhydrous bases?
glycerol monostearate and glyceryl monooleate
-very weak emulsifying capacity
cholesterol
-commonly used in absorption bases
What is the use of anhydrous bases?
specialty compounding like HRTs
Describe lanolin as an absorption base.
can take up to 2x its weight of water
acts as W/O emulsifier
What are additives for absorption bases?
antioxidants
penetrations enhancers +/-=same as oleaginous bases
What are the properties of an ideal antioxidant?
effective at low concentrations
stable
soluble in the vehicle
compatible with pharmaceutical excipients and wide range of drugs
odourless, tasteless
What are the compounding techniques for absorption bases?
same as oleaginous bases (fusion or incorporation)
What is the levigating agent limit for absorption bases? What is the difference in levigating agent compared to oleaginous bases?
5% of the final formulation
hydrophilic levigating agent (glycerol, propylene glycol) can be used
-not used for oleaginous bases
Describe emulsifying bases.
water washable bases (water miscible)
anhydrous bases containing O/W emulsifying agents
cream-like appearance
self-emulsifying
emollient
What kind of emulsion is formed when you add water to an emulsifying base?
O/W
Which base is a soap replacement?
emulsifying bases
What are the main components of emulsifying bases?
all liquid, semisold, and solid excipient same as for oleaginous bases
-fats and fixed oils
-mineral oil
-petrolatum and white petrolatum
-waxes
What are additional components for emulsifying bases?
O/W emulsifiers, mostly surfactants
What are the additives for emulsifying bases?
same as oleaginous bases
-antioxidants
-penetration enhancers +/-
What is the compounding approach for emulsifying bases?
fusion method is more commonly applied
incorporation technique is NOT frequently used to prepare primary bases but can be used for incorporating solid APIs to form final formulations
What kind of levigating agents are used in emulsifying bases?
hydrophilic levigating agents (glycerol or propylene glycol)
emulsifying base can be used as levigating agent in most final formulations
What are the main components of a cream base?
oil phase: liquid, semisolid, solid excipients used for oleaginous bases
-fats and fixed oils
-mineral oil
-petrolatum and white petrolatum
-waxes
PLUS water phase
What are the additional components for cream bases?
emulsifying agents, mostly surfactants
Describe w/o emulsions.
greasier than o/w emulsions
non water washable
emollient, cleansing action
capable of absorbing oil-soluble compounds from skin
Describe o/w emulsions.
water washable
soft
non-occlusive
moisturizing (increases water content–>restores hydration of the skin)
more commonly seen medicated creams are o/w emulsions–>used as drug carriers since it allows higher penetration of drug compounds
What are the additives for emulsions?
antioxidants (oil and water soluble)
penetration enhancers +/-
preservative
humectants
What kind of bases are readily attacked by bacteria and fungi?
topical bases that contain aqueous phases, carbohydrates and proteins
What can microbial growth do to a formulation?
spoil the formulation
-toxic hazard
-source of infection
What is the universal preservative?
there isnt one
-not all preservatives will be compatible with the API
What are the essential requirements for preservatives?
compatible with all ingredients
stable to heat and prolonged storage
non-irritant
non-sensitizing to human tissue
What is the role of humectants?
prevent product from drying out
-withdraw moisture at high concentrations
-increase the hydration of the skin at low concentrations
Differentiate between the oil-soluble and water-soluble antioxidants.
oil-soluble:
-BHT and BHA
-alpha tocopherol
water-soluble:
-ascorbic acid
-sodium bisulfite
What are the compounding methods for cream bases?
method 1: fusion
1. hydrophobic components melted together (start with lowest mp)
2. hydrophilic components dissolved in the water phase and heated 5C higher than oil phase
3. water phase added to oil phase gradually with constant stirring
4. cooled with constant stirring until congealed
method 2: incorporation
-mixing of one semisolid formulation into another (geometric dilution)
Describe lotions.
emulsions, most cases are o/w but can be w/o
key ingredients similar to creams (aqueous and oily phase, emulsifying agent)
Where are lotions typically applied?
hairy areas like the scalp (less viscous=easier to spread)
What are pastes?
oleaginous base with 20% or more solids suspended in base
-different consistency
What are the main components of the base for pastes?
hydrocarbon bases: all liquid, semisolid and solid excipients used for oleaginous bases
-fats and fixed oils
-mineral oil
-petrolatum and white petrolatum
-waxes
Are pastes water washable?
non water washable
-20-50% powder dispersed in fatty base
-very stiff consistency (localize material to defined areas of the skin)
-form a thick impermeable layer on skin (protective action)
What are the compounding methods for pastes?
fusion: used to prepare base
incorporation: method of choice for final formulation
-on glass slab due to thickness
True or false: it is practical to use a levigating agent for a paste
false
What are the properties of hydrophilic bases?
water washable bases
condensation of polymers of ethylene glycol
contain water-soluble components
properties:
-ointment like consistency (soften or melt on skin)
-non occlusive, mix with skin exudates
-do not stain clothes (greaseless)
-non irritant
-chemically stable
-cannot take up more than 8% water
What are the incompatibilities of hydrophilic bases?
phenols, iodine, KI, tannic acid, silver, mercury and bismuth salts
quaternary ammonium compounds and parabens (reduced preservative activity)
inactivate bacitracin, penicillin
What are the advantages of hydrophilic bases?
anhydrous–>useful for drugs that hydrolyze
good patient compliance (non staining, non occlusive)
What are the additives for hydrophilic bases?
antioxidants
penetration enhancers +/-
no preservative or humectants because they are anhydrous
What kind of antioxidants are used for hydrophilic bases?
water-soluble
-ascorbic acid
-sodium bisulfite
What are the compounding methods for hydrophilic bases?
mainly fusion
-all PEG components should be liquidated for mixing
-components are melted together, cooled with constant stirring until congealed
-melting: start with lowest melting point
Describe gels.
water washable bases
liquid-rich, two-component semi-solid colloidal systems
natural or synthetic polymers form a 3D matrix throughout a hydrophilic liquid
What are the properties of gels?
dissolve in water
good for hairy areas
good for oily skin textures
water-soluble drugs are easily incorporated either dissolved in the aqueous phase or dispersed in gel
What are the main components of gels?
natural gums
-tragacanth, agar, pectin, alginates
semi-synthetic or synthetic polymers
-methylcellulose, etc
What is the issue with using natural gums for gels?
hazy appearance
high stickiness
microbial contamination
What is an emulgel?
emulsion either o/w or w/o which are incorporated into a gelling agent
makes gels as suitable dosage form for hydrophobic drugs
allows dual control of the drug release from formulation
What are the additives for gels?
antioxidants (water-soluble)
penetration enhancers +/- (like propylene glycol)
antimicrobial preservatives
humectants
What is the compounding method for gels?
hydration
-full hydration is slow, most of the time takes 24hrs
-exact method depends on the type
What is Plastibase?
gelled mineral oil by addition of polyethylene
unctuous base (stains, difficult to remove)
consistency remains unchanged over a wide temperature range
drugs tend to release faster from Plastibase than petrolatum
What temperature destroys the gel structure of Plastibase?
> 90C
