Opthalmic Drug Administration Flashcards
Label the following diagram.
Describe the outer layer of the eye.
- segment of two spheres: cornea and sclera
- transparent cornea forward 1/6 of eye
- in front of iris and pupil
- innervated densely with sensory nerves
- refracts and transmits light to lens and retina
- protects against infection and damage
- sclera 5/6, tough fibrous tissues
- protects eye from internal and external forces (intraocular pressure of the eye)
- maintains shape
- dense connective tissue = white of eye
Describe the conjuctiva.
- thin, transparent mucous membrane
- covers visible part of eyelid - sclera
- optic nerve emerges from sclera
What are the surfaces of the cornea and conjunctiva covered by?
- film of tears produced by lacrimal gland
- lubricates eye surface
- protection from chemicals, microbes, airborne solid particles
- 3 layers
- mucuous layer
- interacts with epithelial cells of cornea
- each blink = spread of tear film
- aqueous layer
- electrolytes, proteins, glycoproteins, biopolymers, glucose, urea
- superficial lipid layer
- sterol esters, wax esters and fatty acids
- dynamic equilbirium in pre corneal tear film (production, evaporation and drainage)
What are the three chambers of the eyes?
- anterior
- between cornea and iris
- posterior
- between iris and lens
- vitreous cavity
- 80% of eye
- transparent, colourless and gelatinous mass
- between lens and retina at back
- 98% water - 2% collagen fibrils, hyaluronic acid, protein, inorganic salts, glucose
aqueous humour fills anterior and posterior chambers - clear, colourless and watery fluid
aqueous humour leaves anterior chamber via conventional and unconventional pathways
What happens if the aqueous humour cannot leave anterior chamber?
eg if exit blocked
fluid accumulates = increased pressure = glaucoma and damage to optic nerve
What are the main routes of ocular drug delivery?
- cornea
- topically administered drugs reach aqueous humour
- blood retinal barrier (BRB)
- restricts entry of drugs from systemic circulation into posterior segment of eye
- retinal pigment eipthelium (RPE) - outer
- solutes and nutrients from choroid to sub-retinal space
- retinal capillary endothelium (RCE) - inner
- junctions between cells mediate highly selective diffusion of molecules from blood to retina
- retinal homeostasis
- intravitreal delivery
- inj into back of the eye (vitreous chamber)
What are the barried to ocular delivery?
- aqueous humour into systemic uveoscleral cicrulation
- aqueous humour outflow through trabecular meshwork and Schlemm’s canal
- channel in eye that collects aqueous humour from anterior chamber and delivers into bloodstream via anterior ciliary veins
- vitreous humour - diffusion into anterior chamber
- posterior route across BRB
Discuss the osmolality of the eyes.
- determine by conc of salt in lacrimal fluids
- inorganic ions in tears: Na, K, Ca, Cl, HCO3- - control osmotic pressure of intra/extracellular fluids
- healthy non dry eyes - 303mmol/kg at daytime
What is dry eye syndrome?
tear film hyper osmolality
What are the complications of hypotonic ophthalmic solutions?
corneal eipthelium more permeable = water flows into cornea = oedema
irritating to eye, increased production rate of tears
Describe the method of adjusting tonicity.
- identify reference solution and associated tonicity parameter
- determine contribution of drugs and additives to total tonicity
- determine amount of NaCl needed by subtracting contribution of actual solution from reference solution
Describe the pH of tears.
- neutral
- controlled by CO2, HCO3 and proteins, acidic tear prealbumin
- buffer capacity is low but significant
What happens if an acidic or basic solution instilled in eye?
- cannot be neutralised by tears
- reflex tears generated to dilute the administered drop and eliminate it
What are the different types of tears?
- basal tears
- constant tears, protect cornea
- emotional tears
- reflex tears
- irritation from foreign particles
Describe the ph of opthalmic formulations?
- eye can tolerate topical formulation of pH 3.5-7
- preferred: closest to 6.9-7.5
- reduce discomport and associated increased lacrimation
- important for drug ionisation (solubility/permeability) and product stability
How can you maintain the pH of a opthalmic preparation at 4-5?
use of weak acidic buffer
eg acetic acid/ sodium acetete buffer or
citric acid/sodium citrate buffer
borate and phosphate buffers
Why are viscosity enhancers used in opthalmic preparations?
- prolong drug retention in pre-corneal tear film
- enhance drug absorption
- reduced drainage rate
- thickness of precorneal tear film increased
- drag water
- stabilise aqueous layer as they spread over the corneal surface on blinking
- increased volume act as a reservoir of drug
What are examples of viscosity enhancing polymers used in opthalmic preparations?
- water solublepolymers
- poly(vinyl) alcohol
- poly(vinylpyrrolidone)
- cellulose derivatives
- methylcellulose
- hydroxypropyl methylcellulose
- carboxymethyl cellulose (0.2-2.5%)
- poly(ethylene) glycol 0.2-1%
What is the surface tension of a healthy eye?
43.6-46.6 mN m-1
What happens if a solution with lower surface tension of lacrimal fluid is adminstered to the eye?
- destabilises tear film
- disperses lipid layer into droplets that are solubilised by the drug or surfactant in formulation
- in a healthy eye, oily film reduces rate of evapoation of underlying aqeuous layer
- once lost, dry spots formed = painful and irritant
What is the role of surfactants in opthalmic preparations?
solubilise or disperse drugs
What is the best type of surfactant to use in opthalmic preparations?
non-ionic
cationic binds to cell surface membrane (-) = toxic
eg polysorbate 20, polyoxyl 40 stearate
What are the downsides of using a non-ionic surfactant in opthalmic formulations?
- remove mucus layer
- disrupt tight junctional complexes of cornea
- interact with polymeric substances (viscosity enchancers) in the preparation
- reduce the efficacy of preservatives
conc of surfctant important
- drug solubility
- safety and patient tolerance
- high conc = foaming upon manufacturing and shaking
What are sterility requirements of opthalmic preparations?
- must be sterile at time of filling and closing in sealed container
- terminal sterilisation preferred
- if filtration: pore size is 0.22mcm
- raw materials should be sterile, whenever possible or should meet low bioburden control limit
- containers must be labelled with duration of use once opened
What are requirements of preservatives in opthalmic preparations?
- included in multi dose containers
- destroy and inhibit microorganisms growth
- not to be used for intraocular administration = causes irritation
- broad spectrum anti-microbial activity (against gram +/- bacteria)
- exhibit compatability and stability with all ingredients
- harmless to ocular tissue
What are examples of preservatives used in opthalmic preparations?
- benzalkonium chloride
- 0.004-0.02%
- quaternary ammonium salt
- repeated admin. = epithelial toxicity
- phenylmercuric nitrate
- organomercury compound
- powerful antiseptic and antifungal
- low conc
no preservatives in single dose units
What are labelling requirements of opthalmic preparations for hospital use?
- volume of contents - should not exceed 10mL
- official name of preparation
- conc of API (%w/v)
- name and conc of preservatives
- directions
- “sterile until opened”
- “to be used for one eye of one patient only” if patient named, what eye?
- “use with care to avoid contamination during use”
- “to be discarded _ after first opening” (one week for hospital, at end of day for outpatient department use)
- storage requirement
- expiry date
- batch and product license number
- POM or P
- name of patient (hospital ward)
- date of issue
- “for external use only”
- “keep out of reach of children”
- name and address of supplier
What are labelling requirements of opthalmic preparations for hospital use?
- official name of preparation
- conc of API when monograph allows variable conc
- directions
- “sterile until opened”
- “use with care to avoid contamination during use”
- “to be discarded one month after first opening container”
- storage requirements
- name of patient
- date of dispensing
- “keep out of reach of children”
- “for external use only”
- name and address of supplier
Describe the eye drop containers used.
- glass bottles
- amber coloured, vertically ribbed
- neutral glass or soda glass
- fitted with phenolic plastic screw cap (neutral glass dropper tube fitted with natural or synthetic rubber teat)
- or complete dropper clsure may be sterilised - supplied separately
- suitable plastic containers
Describe the limitations to the use of rubber teats for opthalmic prep.
- may be incompatabile with benzoalkonium chloride
- storage limited to 3 months
- slightly permeable to water vapour
- gradual loss of water for prep occurs
- complete dropper assembly should be supplied seperately
- before issue for use, dropper asssembly should be echanged with plain phenolid cap with silicone rubber linear
- readily breakable seals
How do you consel patients on eye drops?
- if 2 eye drops, wait 5-10 between
- eye drops before ointment
- wash hands before
- keep in a cool dry place away from heat
- dont let tip touch eye
- close eyes after administration
