nasal/ear/eye delivery Flashcards
name the 4 liquid filled compartments of the eye
outside eyeball, behind cornea, between iris and lens, behind lens
structures of the eye involved in ophthalmic delivery
eyelids- removes debri
cornea- no blood vessel, delicate but repairs quickly, multi-layered
tears wash eye continually
^all protective/cleaning mechanisms
describe the internal structure of the eye
4 fluid filled regions, only tear chamber and anterior are accessible by topical dose forms (eg. eyedrops), vitreous chamber requires systemic drugs/direct injection
common targets of eye delivery
tear deficiency, bacterial/viral infections, reduction of inflammation/redness, glaucoma, analgesia, pupil dilation, diagnostic dyes
problems with eye delivery and why
very low bioavailability and poor absorption
caused by
drainage- most of eye drop dose drained into nose/swallowed
higher dose dont have higher ocular conc
blinking/rubbing eyes- increase rate of drainage
protein binding
schlera well vascularised- diffusion drugs removed into bloodstream quickly
cornea is a barrier
why is the epithelial layer a major barrier to water soluble drugs
it has tight junctions
describe the formulation design for eye delivery- pH/buffering
buffers can be used to get drugs into a suitable ionisation state for absorption, acidic pH causes more discomfort, corneal damage in pH outside of 3-11
describe the formulation design for eye delivery- tonicity
tears are 0.9% NaCl, isotonic is the best, 0.6-2% NaCl is tolerable
why are eye delivery usually single dose units
minimise cross infection
describe the formulation design for eye delivery- multi dose containers
more convenient but must contain preservatives, sensitivity with long term use
describe the formulation design for eye delivery- irritancy/toxicity
everything in contact with eye gets tested, FDA in vivo test in rabbit eyes, some preservatives
describe the formulation design for eye delivery- preps for eye surgery
no preservatives, safe as it penetrates eye interior, isotonic, neutral pH, single dose
3 formulation types of eye delivery
eye drops- transient effect, viscosity agents increase residence
eye ointment- more prolonged effect, better absorption but causes blurred vision, useful for non aq drug and eyelid problems
inserts- collagen or polymer base
components of ear wax
fatty acids, lipids, polypeptides, debris, epithelial cells
what is earwax
ear canal gland secretions that dry to give a water repellent coat, hydrophobic wax
describe structure of eustachian tube
ciliated, mucus and debris wafted down throat, channel for infection to middle ear, self cleaning
name 3 important structures in ear delivery
ear canal, eustachian tube, eardrum
things that ear delivery is used to treat
excessive earwax/earwax remover, bacterial infection/inflammation, boils, eczema at ear canal entrance, steroid, middle ear, viral/bacterial infection, systemic analgesics/antibiotics (otitis media)
formulation designs of topicals for external ear
non aqueous vehicles used as water in ear canal promotes bacterial growth, sensitivity to PG, oil/surfactants to soften wax as penetration of wax is hard bc of high viscosity and lack of movement, aqueous peroxide to disintegrate wax
what does nasal mean
inside the nose
why use nasal route
treat local infections, access to local receptors to reduce inflammation and excess secretion
methods of nasal delivery administration
nose drops- solutions/suspensions from a dropper bottle
nasal spray- fine droplets/powder for penetration into nasal cavity
creams/ointment- topical for external/internal areas around nostrils
functions of the nose
detection of smell- olfactory receptors in nasal cavity
air conditioning of inhaled air- lots of capillaries, fast flowing, humidifies, water loss though
particle/debri cleanrance- mucocilary clearance
describe stages of mucociliary clearance
particles get trapped in mucus layer, mucus wafted towards larynx by cilia, swallowed
composition of mucus
glycoproteins, salts, water, proteins, lysosymes
properties of mucus (pH and tonicity)
pH= 5.5-7
tonicity= 0.9% NaCl
biopharmaceutical issues with nasal delivery
alters internal environment (mucus secretion/dryness/inflammation)
mucociliary clearance- mucus renewed fast, short residence time for drug action
deposition from sprays depend on particle size, nose drops spread better but sprays penetrate deeper and longer action
systemic absorption- epithelium permeable to drug diffusion but barriers
why is nasal cavity a good target for systemic delivery for difficult drugs like proteins and peptides
permeable and plentiful blood supple
problems with systemic absorption in nasal delivery
mucocilary clearance- short residence time
mucus- binds to drug
enzymes- metabolises drug
irritation/inflammation/damage to nasal mucosa
epithelial barrier requires drug to have an appropriate ionisation state
ways to enhance nasal delivery
absorption enhancers- bile salts/surfactants (damages)
solubility enhancers
prodrugs with good penetration properties- metabolised to active drug after absorption
bioadhesives
microparticulates-increases retention time and bioavailabiltiy
how do microparticulates enhance nasal delivery
increases retention time and bioavailability
formulation design of nasal delivery
sensitive when inflamed so dosage form must be comfortable and avoids stinging, liquid and creams match nasal secretion, neutral pH, non irritating, water vehicle, sterile, drug cant interfere with ciliary clearance
systemic drugs for nasal delivery
hormones- calcitonin, pituitary hormones
migraine- sumatriptan
smoking- nicotine
local drugs for nasal delivery
nasal allergy- antihistamines
decongestants
sympathomimetics- mimic effects of epinephrine/dopamine/norepinephrine/catecholamines
infections
epistaxis (nose bleed after nasal surgery)
