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39 Cards in this Set
- Front
- Back
most common ophtalmic drug delivery system |
eye drops |
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drug absorption from drops can be increased by: |
-waiting 5-10min between drops -compressing lacrimal sac -keeping lids closed for 5 min after instillation |
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eye drops must be: |
sterile, buffered, isotonic |
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advantages of ophthlamic solutions |
-no or little interference with vision -drug can be rapidly taken up by tissues |
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disadvantages of ophthalmic solutions |
-brief contact time between medication and absorbing surfaces
contact time may be increased by adding a viscosity enhancing agent (eg methylcellulose) -viscosity between 15-25cP is ideal for retention and comfort -water is 1cP, veg oil is 50cP, antifreeze 15cP |
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ocular ointment bases |
-typical bases consist of mixtures of petrolatum and liquid petrolatum (mineral oil) -want an ointment that "liquifies" at body temp |
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advantages of ocular ointments |
increase contact time of ocular medication -more drug uptake, better effect |
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disadvantages of ocular ointments |
blurred vision for the first few minutes |
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ocular ointments are effective for what type of drugs? |
highly lipophilic drugs with some water solubility
sometimes a water miscible agents such as lanolin is added to allow water soluble drugs to be incorporated (lanolin is amphiphilic compound - surfactant - get w/o emulsion) |
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ocular bioavailability |
a combination of overflow losses, nasolacrimal drainage and dilution results in very inefficient ocular absorption and typical bioavailabilities in the range o f1-10% -most drugs are in lower end of this range |
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drainage of intraocular fluid |
10-20% through uveoscleral pathway (uvea = cornea, ciliary body, iris)
80-90% through trabecular meshwork and Schlemm's canal 2-3uL/mL to episcleral vein (to systemic circulation |
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transcornial diffusion |
corneal abs represents major mechanism of abs for most drugs
-abs of drugs is rate limited by cornea -cornea composed of 3 major diffusion barriers: epithelium, stroma, endothelium -epithelium is rate-limiting barrier for abs of hydrophilic drugs because it contains high lipid content (100x more than stroma) -stroma (mostly hydrated collagen is rate-limiting barrier for very lipophilic drugs -endothelium is lipoidal in nature, but does not offer a significant barrier to transcorneal diffusion of most drugs |
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layers of cornea |
1200um:
epithelium (hydrophobic) bowman's membrane stroma (hydrophilic) descemet's membrane endothelium (hydrophobic) |
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losses of drug during disposition in the eye |
precorneal area: -conjunctival-scleral binding -tear protein binding -nasal lacrimal drainage
cornea: drug-protein binding -enzyme degradation
anterior chamber: -drug-protein binding -enzyme degradation -trabecular network drainage |
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ophthalmic suspension |
dispersion of finely divided solid drug particles in an aqueous vehicle containing suspending and dispersing agents -surrounding soln is saturated w drug -drug is absorbed from soln which is replenished from solid particles |
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advantages of ophthalmic suspensions |
contact time and duration of action exceeds that of soln |
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disadvantages of ophthalmic suspensions |
cosmetically not the most attractive
solid drug particles may irritate the eye, leading to excessive tearing and removal of the dose -particles should be less than 10um -careful of temp changes and Ostwald ripening (crystal growth) |
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ocular diagnostic drugs |
Fluorescein dye -available as drops or strips
uses: -stain corneal abrasions -applanation tonometry -detecting wound leaks -nasolacrimal duct (NLD) obstruction -fluorescein angiography
caution: -stains soft contact lenses -fluorescein dropscan be contaminated by Pseudomonas sp |
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principles of formulation of ophthalmic delivery systems |
1. Tonicity 2. Sterility 3. pH and buffers 4. Viscosity 5. Surfactants: wetting agents |
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Tonicity (ophthalmic formulations) |
eyes can tolerate equivalents of 0.5-1.6% NaCl without great discomfort -adjust ophthalmics to isotonicity wherever possible |
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examples of tonicity agents |
NaCl Dextrose Glycerin |
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examples of preservatives |
benzalkonium chloride phenylethyl alcohol chlrobutanol phenylmercuric nitrate parabens
EDTA often added to enhance effectiveness of preservatives |
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pH and buffers (ophthalmic formulations) |
stability -optimal stability for most weak base salts is low pH (2-4) irritation -pH of tears is 7.4 -irritation occurs at pH > 8 or <6 solubility -for weak base salts, solubility is increased at lower pHs
optimizing pH: stability is most important consideration but may have to compromise if pH is too low -tears have some buffering capacity and can raise pH of drug soln |
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examples of buffers |
boric acid phosphate |
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viscosity (ophthalmic formulations) |
increase viscosity: -increase contact time on cornea -decrease nasolacrimal drainage rate -increase abs and bioavailability |
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examples of viscosity agents |
methylcellulose hydroxymethylcellulose polyvinyl alcohol gellan gum |
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examples of surfactants (wetting agents) |
nonionics only: polysorbates |
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Pluronic PF127 |
thermosensitive polymer -viscous liquid at room temp, turns into semisolid transparent gel at body temp
driving force: water-polymer interaction, phase change at lower critical soln temp (LCST)
PEO-PPO-PEO triblock copolymer |
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how gel dissolution relates to drug release |
the higher the drug dissolution, the more drug released |
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Ocular DDS Reservoir Devices - rate controlling membrane |
-assume that the concentration in the reservoir is very high (assumed constant) and the concentration in the sink is very low (~0) -after an initial unsteady period, we will reach steady state -zero order release (constant rate of drug release from device) |
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what type of drugs are good to use for intraocular inection therapy? |
if can't get drug in another way (eg Pilocarpine goes in so well from patch or eye drops so don't need injection)
commonly used: -hydrophilic antibiotics -antibodies |
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example of intracameral injection |
intracameral acetylcholine during cataract surgery |
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examples of intravitreal (intraocular) injection |
-intravitreal antibiotics in cases of endophthalmitis -intravitreal steroid in macular edema |
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Peri-ocular injections |
-bypass the conjunctival and corneal epithelium -good for drugs with low lipid solubility (eg penicillins) |
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drawbacks of intraocular injections |
-poor pt acceptablity -rapid drug elimination from vitreous humor (to systemic circulation) -potential retinal toxicity -hazards associated with repeated intravitreal injections (clouding of vitreous humor, retinal detachment, lens damage, endophtalmitis)
to minimize these, frequency of injection should be reduced with adequately designed controlled release systems (once or twice per year) |
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components of retina |
some blood vessels photoreceptors (rods/cones) retinal pigment epithelial cells Bruch's membrane Choroidea (blood vessels) Sclera |
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Vitrasert |
-tablet-shaped implant containing 4.5mg ganiclovir and coated with polyvinyl alcohol and ethylene vinyl acetate -release takes place over 5-8 mths by passive diffusion through a hole in the system (not degradation!) -indicated for site-directed intravitreal therapy of CMV (cytomegalovirus) retinitis in pts w AIDS |
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components of Vitrasert |
-impermeable polymer (ehtyl vinyl acetate) -permeable polymer (polyvinyl alcohol) - regulates release of drug -ganiclovir -suture tag |
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magnetic stem cell delivery |
stems cells that can take up nanoparticles -put magnet under plate -cells move to magnet and accumulate -cells filled with magnet nanoparticles (magnitized stem cells) -inject into pt -magnet at back of eye -attract particles close to retina |