ic8 - pharmacy technology Flashcards
what is the nostril separated by
septum
what are the three main regions of the nasal cavity
nasal vestibule, respiratory region and olfactory region
[nasal vestibule] hairy, first contact with external environment thus hair helps to keep out large particulates
[respiratory region] has three turbinates (superior, middle, inferior) which creates a vortex when you breathe in air
[olfactory region] located in olfactory recess (upper most area) which has direct connection to CNS via olfactory neurons, region is highly vascularised despite small surface area of approx 15cm2 (approx 10% of nasal surface area)
what kind of cells does the olfactory epithelium comprise of and what is its function
olfactory epithelium lined with epithelial and mucosal cells where drugs and small molecules will solubilise into then interact with receptors
what kind of cells does the respiratory epithelium comprise of and what is its function
respiratory epithelium lined with ciliated columnar cells that have a large surface area to enhance drug delivery once it solubilises in mucus layer, it can then interact with the cells via various transports to be shuttered across to interact with blood vessels and the trigeminal nerve which is another direct route to the brain
what kind of permeation routes allows for access to CNS from olfactory and respiratory regions
transcellular transport, paracellular transport and intraneuronal transport
[transcellular] through active mechanisms through the cells, slow (approx 13h)
[paracellular] rapid uptake, passive transport through gaps between cells, high turnover (always being recycled) of olfactory sensory neurons that can leave more gaps
[intraneuronal] shuttering across neurons
what is the property of olfactory neurons that helps with paracellular transport
high turnover rate of olfactory neurons which can leave more gaps between cells to help facilitate paracellular transport
what are the advantages of intranasal delivery
non invasive, can be self administered, bypasses hepatic first pass effect (where there is metabolic enzymes that breaks down certain drugs thus decr effective conc of drug and decr therapeutic outcome), shorter onset of effect due to close proximity to CNS (which is our target site of action)
what are the inherent barriers to intranasal delivery
nasal epithelial layer, nasal mucus of approx 5microm, metabolic enzymes, efflux pumps, hair, volume
[nasal epithelial layer] layer of cells the drugs have to diffuse through to get access to the brain
[nasal mucus] viscous aq layer, drug movement here is slow, drugs are often water based
[metabolic enzymes] present in mucus layer (though not extensive) and will breakdown substances
[efflux pumps] present in mucus layer which ejects certain foreign material
[hair] drug has to be delivered past hair else it causes irritation and risk being sneezed out which results in loss of product and thus decr therapeutic effect
[volume] small volume, esp olfactory region, have to balance conc and vol bc risk of irritation
what rule determines the characteristics of an ideal drug candidate and what are the components of this rule
lipinski’s rule of 5
5 or less H bond donors
10 or less H bond acceptors
<500Da (<300Da for N2B access of hydrophilic drugs, <1kDa for N2B access of lipophilic drugs)
LogP <5
unionised
what are the functions of a delivery system
- make the drug physically manageable
- improve drug solubility
- improve drug absorption
- protect drug from degradation and excretion
- improve drug retention
- reduce s/e (through targeting)
- incr dosing
- reduce freq of administration which can improve pt compliance
what are the types of delivery systems
solutions, suspensions, powders, gels
what is an added advantage of using a gel delivery system
gels have higher viscosity and contains water which can be hydrating, apart from enhancing solubility and delivery of drugs
what are some types of suspensions that can be used as delivery systems
nano/micro emulsions, liposomes, nanoparticles, other lipid based self assembled structures
what are “excipients”
ingredients aside from active ingredients
are pharmacologically inert
have different functions
what must be done when including excipients into delivery systems
important to test compatibility of excipients with active ingredients
list examples of some nasal sprays, nasal powders and nasal gels currently on the market
nasal sprays: sumatriptan (imitrex) for migraine, midazolam (nayzilam) for seizures, naloxone (narcan) for opioid overdose
nasal powders: sumatriptan (xsail) for migraine
nasal gels: in development
what are some common excipients of nasal sprays and list some examples for each type of excipients
diluent, buffer salts, preservatives, stabiliser/ co-solvent, permeation enhancers, viscosity modifiers
what might a viscosity modifier do for a drug
increase viscosity of drug formulation such that it can retain on epithelial layer and be less affected by flowing mucus thus providing enough time for drug to diffuse across the membrane
what are the considerations for excipients (pH, tonicity, volume, container, storage)
pH 4-7.4
tonicity 300-700mOsm
volume max 200microL
container vessel material should not have chemical or physical interactions with drugs and excipients, protects the formulation from contamination and degradation
store in cool, low moisture environment, but not in fridge or freezer
opaque
what are in situ gels and list some common polymers that would be used to formulate in situ gels
in situ gels are gels with low viscosity solution initially but viscosity increases once administered due to activation by stimulus
stimulus can be salt conc, pH, temp etc
(eg. low viscosity at pH4 but when pH5 incr by 3x)
common polymers used are carbopol 934, hydroxymethyl cellulose K4M, buffer components (triethanolamine, potassium dihydrogen orthophosphate, NaOH), hydroxypropyl-beta-cyclodextrin, paliperidone, pluronic F127, chitosan
what is the benefit of in situ gels
it allows for longer retention on epithelium which helps increase absorption
what is the moa of sumatriptan and its indication
serotonin receptor agonist, induces inhibitory action in CNS to relief migraine
indicated for migraine
what is the dosing for imitrex
imitrex is sumatriptan
dosed at 5/10/20mg in 0.1mL, one to two sprays into one nostril (max 40mg in 24h)
another spray may be used after at least 2h since last spray
what is the composition and role of each ingredient in imitrex
imitrex is sumatriptan
monobasic potassium phosphate NF – a conjugate acid base pair to serve as buffer
anhydrous dibasic sodium phosphate USP – conjugate acid base pair to serve as buffer
sulfuric acid NF – buffer
NaOH – buffer
purified water USP – diluent to bulk up formulation
note no preservatives bc single use
