drug delivery to the eye

• What are the four modes of administration of a drug and what do they include?

  Topical - ocular, nasal, epidermal and direct application to epithelium.

  Enteral - (via GI tract) oral, sublingual/buccal and rectal

  Parenteral - (avoid GI tract) injection, infusion and implant.

  Inhalation
• What is topical administration used for?

  most common route

  primarily anterior segment
• When would the systemic route be used?

  makes use of ocular blood supply
• What are some examples of systemic drug route drugs?

  Oral acetazolamide

  Flucloxacillin

  iv fluorescein
• What are the direct injection routes?

  subconjunctival

  retroblubar

  intravitreal

  EOM
• What are some examples of direct injection drugs?

  Botulinum toxin A

  Ranibizumab

  aflibercept
• The eye similar to the brain is protected from what and therefore what exists?

  From the systemic circulation by tissue and cell barriers: the tight-junction of the ciliary body epithelium; the retinal pigment epithelium and endothelial cells of the iris; and the retina.

  Therefore, anatomic and dynamic barriers for drug penetration into the eye tissues exist.
• What does the absorption factor in pharmacokinetics do?

  molecular properties of drug

  drug formulation

  functional status of tissue forming barrier
• What is the distribution factor in pharmacokinetics determined by and what can it reach?

  primarily determined by tear film and corneal epithelium, aqueous humor, ciliary body and uvea
• What does the metabolic factor of pharmacokinetics do?

  ciliary body major source of drug metabolizing enzymes.
• Describe the excretion factor in pharmacokinetics in ocular drugs.

  Drugs absorbed through cornea leave via uveoscleral route

  Bloodstream is responsible for removing drugs and drug metabolites

  Also via aqueous humor into episcleral vessels
• When the eye drop is instilled, what happens with systemic absorption and elimination?

  Majority spills onto lid and periocular skin

  or retained & drained via the puncta, into nasolacrimal duct

  Absorbed by the nasal mucous epithelium and into the systemic circulation, or blown out the nose
• When the eye drop is instilled, what happens with ocular absorption and elimination?

  <10% absorbed by corneal and conjunctival epithelium.

  Peak concentration 15-30 mins after instillation

  Some absorption after few mins

  Diffuses into the corneal stroma, aqueous humour, iris or further to ciliary body & uvea
• Define bioavailability.

  extent and rate to which the active drug ingredient is absorbed and therefore available at the site of drug action.
• What type of factors may influence ocular drug absorption?

  eye factors

  drug factors
• What are some eye factors that may influence ocular drug absorption?

  tear volume and drainage

  tear flow

  reflex lacrimation

  ocular health

  patient age

  amount of pigment within the eye
• What are some drug factors that may influence ocular drug absorption?

  active ingredient

  excipients
• How does tear volume affect ocular drug absorption?

  Fluid capacity of conjunctival sac 4-5x << volume of eye drop

  Increasing drop size/number of drops will not increase more medication on the cornea

  Altered tear volume
• How does tear drainage affect ocular drug?

  Speed depends on puncta and nasolacrimal duct patency.

  increased with blinks
• How does tear flow affect ocular drug absorption?

  Normal rate 0.5-2.2µl /min

  Increased tear flow will reduce drug concentration available

  Reflex lacrimation stimulated by ocular irritation (often caused by eyedrops)

  Drug wash-out - diluting drug in contact with cornea
• How can a compromised cornea affect ocular drug absorption?

  increased and quicker drug

  absorption
• In a phakic eye, what acts as a barrier between the aqueous and vitreous humours?

  crystalline lens
• What is an aphakic eye and how is exchange effected in this eye?

  It is an eye that lacks a crystalline lens it increases the exchange between the humours
• What is a pseudophakic eye and how does it affect exchange?

  The natural lens is extracted and replaced with intra-ocular lens (IOL)

  it acts as a barrier and the exchange will be altered.
• How does an increased patient age affect ocular drug absorption?

  more likely to have reduced tear drainage

  less drug wash-out ore likely to have dry eye

  Reduced corneal integrity = increased absorption
• What factors in neonates and infants increase the likelihood of systemic absorption?

  decreased tear production

  immature nasolacrimal drainage

  immature metabolic enzymes
• Why is it that newborns and infants are at a risk with thin membranes in the eyes?

  drug absorption and corneal permeation may be more rapid in these patients
• When the target site of an eye drop is beyond the cornea, for example the ciliary body or pupil sphincter with an anti-muscarinic, pigmentation will influence the bioavailability at the target site.
• How does darker irises having increased melanin pigmentation affect ocular drug absorption?

  Increased absorption at iris

  Less available for target site

  Prolonged effect as drug slowly released by melanin
• How do the lipophilic drugs penetrate the corneal epithelium?

  By crossing membranes of cells whereas lipophobic are not soluble in fat/lipids
• Why are hydrophilic drugs more suitable to parenteral administration?

  Hydrophilic drugs are water soluble , poorer absorption characteristics , in terms of eyedrops that cannot penetrate the corneal epithelium
• How can the ionisation or the pH of the active ingredient affect drug absorption?

  The pH and ionisation status of a drug will dictate how quickly it penetrates the ocular surface barriers. Most drugs are either weak bases or weak acids.

  If a mildly acidic drug is instilled into contact tissue of a similar mild acidic pH, the drug remains un-ionised.

  Unionised drugs will enter the bloodstream easier and cross barriers such as the corneal epithelium better than drugs that are ionised.
• What is the ideal pH doe eye drops and what are the side effects if it is not?

  7.4 - around the same of tears

  patients may experience irritation, nipping on instillation which in turn will increase reflex tearing and reduce contact time on the eye
• Why are excipients added to the product?

  To address various limitations of the active ingredient
• What can excipients be used for?

  They can be used to stabilise the pH of the active ingredient as well as altering other properties of the drug to improve absorption, patient comfort
• What do some additional excipients include?

  Chelating agents, surfactants, preservatives and viscosity agents
• What do polymers do?

  Slow down the washout caused by reflex lacrimation, improving drug delivery to the eye and providing lubrication
• Why are excipients added to a product?

  To address various limitations of the active ingredient
• What are the excipients in prednisolone used as and what does it do?

  These excipients are used as preservatives - to reduce risk of microbial growth, to stablise pH of the and to improve comfort for the px
• What are some common drug forms/delivery system used in eyecare?

  aqueous solutions

  drops

  gels

  ointments

  ophthalmic wafers or strips

  sprays

  inserts