Pharm Quiz 3 Flashcards
epidermis
1st layer 60-800 microns eyelids - 80 microns palms/soles - 600 microns Contains: melanocytes (gives skin color) and langerhans cells (immune response)
dermis
between epi and subq layers can get blood circulation once in dermis 2-5 microns contains the pores, sweat glands, muscles, blood vessels, nerve endings, receptors deep dermis - pain transdermal - minimum pain
sebaceous gland
deeper tissue under dermis
oily/waxy material
sweat glands
regulates temperature/lubricates skin
skin function
two-way barrier, prevents absorption/loss of water
stratum corneum
upmost layer 15-25 layers, shed upwards 10-15 microns flattened and anucleated (no nucleus) and top is where dead cells are
cell type in stratum corneum
corneocytes/ keratinocytes
composition of stratum corneum
protein (keratin) 40%
lipids (ceramide, cholesterol) 20%
water 40%
shape of stratum corneum
flat
2 functions of stratum corneum
- protect underlying skin layers
2. barrier to water loss and absorption of harmful substances
langerhans cells
diagnostics, target immune system
melanocytes
pigmenting cells in the skin
melanoma
skin cancer, uncontrolled growth of melanocytes
rate limiting layer
stratum corneum
transcellular is the same as ____
intracellular
trans-appendendageal is good for
through the pores- not uniform throughout the body
paracellular
between two cells
when does a drug penetrate through the skin? (6)
- hydration of SC (inc drug absorb, like wet under bandaid)
- thickness at different anatomical sites (epi layer)
- heat (also inc drug absorb)
- inflammation (if skin compromised)
- age (ceramide)
ceramide _____ as age increases, so absorption would ____ - WHY?
ceramide decreases as age increases- increases space in SC- so absorption would increase
ceramide is the main component of SC - reduced lipids
topical delivery
thin film on skin without aggressive rubbing
main functions of topical formulations
- skin hydration
- protective (or barrier) functions
- delivering medication into the skin
skin hydration topical formulation
use emollients/softeners as the base
emollients keeps in moisture (moisturizer)
protective (or barrier) functions of topical formulation
sunscreen, butt paste (remedy for diaper rash)
delivering of med to skin function of topical formulation
for local action
ex: antibiotics/ anti-fungals, analgesics/ steroids
desirable characteristics of topicals
- uniform distribution of drug
- no grittiness
- non-irritating
- pharmacological elegance
- viscosity
technique used to reduce grittiness/size
levigation/filtration
why viscous topicals
more viscous stays on longer
pros topical administration
- highly localized concentration of drug
- non-invasive
- easy to use
cons topical administration
- contact time can be limited
- messy/ greasy
- undesirable systemic absorption possible
- hypersensitivity
ointment - when and why
when: dry/thick scale skin
why: keep moisture in
ex: vaseline
cream - when and why
when: weeping/oozing surfaces/ open wounds
why: absorbs water
lotions - when and why
when: rubbing/ hairy surfaces
why: reduces friction
gels
when: wet oozing rashes/ poison ivy
why: drying/ soothing
ex: aloe
pastes
when: red/itchy/rubbing surfaces
why: thick/stays on longer/ can absorb secretions
ex: butt paste
USP categorized 4 ointment base cattegories
- oleaginous
- absorption
- water-removable
- water-soluble
based on occlusiveness (closes in and prevents escape), fatty, less to more water
methods to prepare most ointments
- incorporation - drug pulverized to reduce size using titration and blenders with slab-spatula, add small amount of insoluble drug, lipid soluble levigating agent (mineral oil) used to wet powder, drug added by geometric dilution
- fusion- heat to liquify, all parts melted, mixed together, heat-labile/volatile compartments at the end
oleaginous bases
“hydrocarbon bases” - longer than 25 carbon in chain length, on application to skin occlusive emollient effect, can remain on skin for a long time w/o drying out, very greasy not easily washed, cannot incorporate water
petrolatum, USP
- purified mixture of semisolid hydrocarbons from petroleum, yellow, melts at 38-60 degrees C, used alone or combo with agents , known as yellow “petroleum jelly”
- oleaginous base
- petroleum jelly
white petrolatum, USP
fully or nearly discolored- bleaching
same purpose but more aesthetic then petrolatum
- oleaginous base
yellow ointment, USP
yellow wax: 50g
petrolatum: 950 g
yellow wax purified wax from a honeycomb of a bee
has a slightly greater viscosity than plain petrolatum
- oleaginous base
white ointment, USP
yellow wax is substituted with white wax (bleached and purified form)
white petrolatum
- oleaginous base
absorption bases
two types: 1. become w / o emulsion 2. are 2/o emulsions
occlusive, not as much oleaginous bases, still not easily removed by water
hydrophilic petrolatum, USP
becomes w/o emulsion base as it permits incorporation of aqueous solution, ability to absorb some fluids
does not have water in formula
cholesterol 30g, stearyl alcohol 30 g, white wax 80g, white petrolatum 860 g
aquaphor
variation of hydrophilic petrolatum and can absorb up to three times its weight in water
Already are a w/o emulsion
Absorption base - variation of absorption base that contains more water. Still poorly washable. Not as occlusive as oleaginous bases
Lanolin, USP
Natural product obtained from wool of sheep, purified wax- like, cleaned and deodorized and decolonized, contains more than NMT 0.25% water. Additional water can be incorporated.
Incorporating a drug into an absorption base
- Either incorporation or fusion - heat
- Use levigating agent
- Final destination of drug/excipient should be considered when determining levigating agent
Water soluble levigating agents
Glycerin, propylene glycol
Lipid soluble levigating agents
Mineral oil
Water- removable bases
O / w emulsions, resemble creams, external phase of emulsion is aqueous, so they wash off easily.
Hydrophilic ointment
Water-removable base
Water soluble base
- no oil component
- completely water-washable and sometime referred to as “greaseless”
- soften with addition of water, large quantities of water cannons be added
- used to incorporate water soluble solids
Polyethylene glycol
Ethylene oxide and water Different grades- numerical designations Corresponds to the avg mol wt. of the polymer used NMT 600-clear odorless liquids Above 1000 - waxlike white materials In between - semisolids (600-1000) Range from 200-8,000
PEG Ointment, NF
Polyethylene glycol 3350-400g (solid)
Polyethylene glycol 200-600g (solid)
Obtain a semisolid ointment
Has water!
Vanishing cream
Large % of water and stearic acid (18 chain length)
After application to skin, water evaporates and leaves a thin film of stearic acid
Creams (uses and pros)
Uses: emollients or medicated
Pros: easy to apply and remove, creams can accept up to 50% water, creams are “softer” than ointments and often preferred by patients, ointments do not remove water from skin, creams can and are used to dehydrate weeping lesions
Gel
Semi-solid systems consisting of drug/excipients dispersed in a jellylike aqueous vehicle consistency due to addition of gelling agent
Synthetic gelling agents
Cellulose derivatives - CMC, HPMC
Carbomers- 934/940 etc. 0.5%-2.0%
Silicone gel
Natural ingredients like tragacanth, aloe
Can be medicated if needed to contain a drug substance
Preservative added due to high water content
Pastes
Contains larger portion of solid making them stiff
Used for protective action and can absorb serous secretions/discharge
- stay in place longer because they are so stiff
Zinc oxide paste
25% zinc oxide
25% starch
In oleaginous base (white petrolatum)
Very firm product, protects skin and absorbs secretions
Microbial testing for all topicals
For most approved dermatological products
Preservative- use when risk of infection is high
More infection when more water- white ointment versus vanishing cream - lanolin vs hydrophilic ointment
Counter irritants
Acts as an irritant on painful zone, attenuated the sensation of pain
Secondary irritant to counter initial pain
Induces local inflammation to relieve inflammation in underlying or adjacent tissues
Keratolytics
Removes excess retain and thin epidermis. Acts as a chemical peel/exfoliant
Improves moisture binding capacity
Ex: salicylic acid
Astringents
Chemical that tends to shrink or constrict body tissues
Astringent medications cause shrinkage of mucous membranes or exposed tissues
Ex: zinc oxide
Protectants
Protects skin from various factors such as moisture, air, sun, chemicals
Base witho or without active ingredient
Ex: butt past, sunscreen
Emollients
Preparations that soften the skin
Usually contain fatty components such as mineral oil, petroleum, or paraffin
Reduces or retards evaporation of water
Oleaginous compounds - occlusive layer
Antibiotics
Skin infections
Prevents minor skin injuries such as cuts, scrapes,and burns from becoming infected
Fingertip method for application
O.5 / finger tip
anderson cascade impactor
mimics drug delivery in the lungs by vacuum pump - examine the drug collected at each plate and equate the amount drug delivered to each area of the lung
MDI
consists of four parts: pressurized container of drug suspension propellent, metered vale to control the dose, actuator that controls opening of spray orifice and dip tube through which drug and propellant flow (propellant not liquefiable gases or compressed gases)
DPI
dry powder inhalers basically function to hold the dose of powder drug. come in multiple forms; the “disc” or the device can hold bulk or individual doses
spacers/holding chambers
plastic tube that connects mouth piece of MDI to reduce amount drug deposited in the upper airway/decrease oral deposition and absorption.
nebulizer
jet or ultrasonic compressor to aerosolize a solution of drug. tubing connects the compressor to the nebulizer cup that is attached to a mouthpiece
advantage and disadvantages of MDI
adv: compact, multi-dose, meters dose, relatively inexpensive, low risk of contamination due to being a closed system and reproducible results
disadv: possible oral deposition of medication, limited dose size, patient drastically impacts drug delivery, limited drug stability
ex: albuterol sulfate
DPI adv and disadv
adv: portable, enhanced drug stability with protein meds, no requirement of propellant, deliver bulk or individual doses
disadv: correct technique must be used, if the powder hits the throat it can trigger a cough reflex and medication is hydroscopic
ex: insulin
nebulizer
adv: drug solutions offere enhanced drug stability, little patient skill required to operate device correctly, large doses admin
disadv: expensive, time consuming, contamination possibility
afrezza
human insulin inhalation powder: administration mimics the early insulin response in health individuals and has a faster onset of action even rapid-acting insulin; must be used in conjunction with a long-acting insulin
adasuve
loxapine- inhalation powder for the acute treatment of agitation with schizophrenia or bipolar 1 disorder in adults; one use container
DPI vs MDI counsel
DPI: have to load the dose,
MDI: press down canister same time you inhale
transdermal delivery
drug traveling through extracellular lipids in the gaps around cells that make up the skin - per-cutaneous route to the dermis
PLO gel works
PLO- pluronic lecithin organogel. organo phase and aqueous phase in a structurally well-defined micellar network. organic phase undergoes spontaneous gelatin after incorporation with the aqueous solution
passive transdermal delivery drug properties
low dosage (<10) low MW (<400) moderately lipophilic
transdermal delivery system
employs the skin to deliver a drug systemically by having the drug pass through the epidermis and enter the dermis
TDS 1st generation
passive patches consisting of small lipophilic drugs that diffuse into the skin
- occlusive, impermeable backing
- adhesive to keep the patch in place
- protective linear for storage and transport that is removed before use
TDS 2nd generation
active patches that have additional enhancers such as heath activators to help speed the diffusion of the drug to the skin
TDS 3rd generation
patches that employ outside forces such as micro-needles or electricity to force the drug into the stratum corneum to deliver larger molecules and less lipophilic drug molecules that oculd not be delivered otherwise- physical methods of electrical current, heat, microneedles
Membrane-Modulated (MM)
- membrane controls delivery
- dysfunction or damage to membrane could result in dose dumping
- small quanitity of drug is in the adhesive layer over the control membrane for a bolus dose
- first gen*
catapress-TTS
(clonidine) MM system
matrix dispersion type systems
drug is dissolved or disperesed with a polymer or polymer gel such as PVP (polyvinyl pyrrolidone) or PVA (polyvinyl alcohol) upon cooling; “dot matrix delivery system”
- prevents dose dumping
- peripheral adhesiveness around the patch
- first gen*
habitrol
(nicotine) Matrix dispersion type system
transderm-Scop
(scopolamine) MM systems
drug-in-adhesive (DIA)
diffusion- controlled systems - stick with finger pressure - release liner separates DIA layer from skin; stronger adhesive than MM or matrix dispersion
acrylic polymer film liner with silicone adhesive or silicone coated film liner with acrylate adhesive
clima pro
(estradiol/levongestrel) DIA
menostar
(estradiol) DIA
nicoderm CQ
(nicotine) DIA
daytrana
(methylphenidate) DIA
duragesic
(fentanyl) DIA
release controlling membrane in MM transdermal patch
adhesive contains small quantity of drug to deliver a bolus dose upon application of the patch. release controlling membrane controls the rate of drug delivery.
matrix dispersion and DIA differ from MM patches
matrix and DIA mechanisms prevent dose dumping. MM don’t. MM patch damaged- dose dumping. dose dispersed in polymer or adhesive in other two types of patches.
scopolamine, nicotine, and fentanyl passive transdermal patches work
high conc in patch, diffuses down conc gradient from the patch into the ski. more than just the dose to be delivered into the patch. sometimes more drug will be leftover in the patch than was delivered to the skin. patches only should be worn for small period of time and disposed properly .
how chemical enhancers/heat helps 2nd gen TDS
helps drug move through epidermis more quickly than from a 1st generation TDS by enhancing skin permeability
chemical enhancers
DMSO: incresases soluble drug in vehicle and disrupts the protein in keratinocytes, increasing the rate of diffusion through the skin
ethanol/methanol and propylene glycol: disrupts the lipid bilayer structure, permeabilizing the stratum corneum and enhancing partitioning in the skin
heat
CHADD system (controlled heat assisted drug delivery): air exposure to iron powder initiates the reaction to generate heat equivalent to 5 degrees increase in room temp
iontophoresis
uses low level electric current to move charged molecules across the skin because the electrical current can be manipulated so can the rate of delivery
ionsys
fentanyl iontophoretic transdermal systemic circulation over a period of 10 minutes. application of electricity to the positively charged drug in the reservoir sends the drug into the skin to the blood vessels of the dermis
instanza
seasonal flu vaccine in Europe. self-admin and uses a 1.5 mm microneedle. does not penetrate the dermis so no pain is felt.
