Ocular Systems Flashcards
What are common eye conditions?
*allergies
*blepharitis
*cataract
*conjunctivitis
*dry eye
*glaucoma
What are physiological barriers of the eye?
*cornea
*sclera
*tear production/blinking- eye drops removed faster
*protein binding/drug metabolism
What is the precorneal volume?
7uL, volumes of 20-30uL can be held before spillage occurs
What physiochemical drug properties should be considered when designing ophthalmics?
*solubility- lipophilicity
*molecular size and shape
*charge
*degree of ionisation
All affect RATE and ROUTE of permeation into cornea
What are the two ways that ophthalmics travel into the eye?
*passive diffusion- transcellularly (lipophilic) or paracellularly (hydrophilic)- both lipophilic and hydrophilic drugs permeate better
*carried mediated active transport-
Does ionised or unionised form permeate lipid membranes of eye easier?
Unionised
Is the corneal epithelium positively or negatively charged and do cationic or anionic drugs permeate better?
Negatively and cationic drugs
What size do particles have to be for ophthalmic drugs?
<500 daltons
Why is chemical form of a drug important in ophthalmics?
Changing salt affects solubility and lipophilicity of drug
How do you fix drugs that don’t meet the desired physiochemical properties?
Use prodrug (converted enzymatically or chemically to parent drug in eye)
What are advantages of using solutions (eye drops)?
*high solution conc can be achieved
*easy to manufacture
*provide better dose uniformity and ocular bioavailability
What is a disadvantage of using solutions?
Rapidly drained from eye
How can the rapid clearance of drug solutions be fixed?
*add viscosity increasing agents to increase tear viscosity
*eg hydroxyethylcellulose
What are water based gels?
Contain polymers so that they are liquid upon administration but gel on contact with eye- increase retention times
Why is there a phase change in water based gels?
*change in temp on contact
*change in pH
*change in ionic strength in tear film
What is an advantage of using water based gels?
*ease of administration
*improved patient compliance
Why would suspensions be used for drug delivery?
*for poorly water soluble drugs
*drugs with poor aqueous stability
What is an advantage of using suspensions?
Prolonged residence time of drug in eye, allowing time for dissolution in years - increased ocular bioavailability
What are disadvantages of using suspensions in eye drug delivery?
*instability issues- dose uniformity, increased particle size with time
*possibilities of degradation during sterilisation process of suspension
What part of the eye are ointments applied to?
Conjunctiva
When are ointments applied and why?
Nighttime- can cause blurred vision
What should be considered when choosing packaging for ophthalmics?
*are materials compatible with formulation and ensure product stability?
*can sterility be achieved and assured for entire shelf life
*do materials meet pharmacopoeial and regulatory standards?
*are containers tamper evident?
* does it offer ease of administration to patient ?
What are the critical quality parameters for ophthalmics?
Ophthalmics are required to:
-be sterile up to point of use
-must comply with pharmacopoeial tests for sterility
What type of sterilisation should be used for ophthalmics?
Terminal sterilisation
What are excipients used for in ophthalmics?
To improve tolerability and compliance
What pH range can eye tolerate?
3.5-9 (7.4 preferred)
Any other- eye irritation
If pH manipulation fails to increase drug solubility, what is the next step?
*Add solubility enhancing materials (glycerin)
*if desired aqueous solubility not achievable, consider oily solution or emulsion
Why is too high of a viscosity not well tolerated in the eye?
Drug diffusion inhibited
Hard to administer
What is an example of an ophthalmic antimicrobial preservative?
Methylparaben
How are ophthalmics sterilised?
*autoclaving- manufactured and packaged under clean conditions followed by sterilisation- moist-heat sterilisation
*filtration- through a circa 1um filter
*production under aseptic conditions- dispersion of sterile therapeutic agent into sterile vehicle and packaging
How do contact lenses work?
Polymers that correct Vision issues from refractive error
What is a complication that can arise from contact lenses?
Microbial keratitis
What are the functions of contact lens solutions?
*soaking- disinfects, maintains hydrated stats (NaCl)
*(re)wetting- hydrates lens, deals with contamination, lubricates (NaCl)
*cleaning- removed ocular debris, dust and bacteria (NaCl)
