Ophthalmic Delivery Systems Flashcards
(22 cards)
What are 3 Ocular Drug Delivery Routes?
- Cornea: topically applied drug to aqeous humour
- Blood retinal barrier: restricts movement of drug from systemic circulation to posterior cavity
- Intravitreal delivery
What are Reasons for Treatment?
- Blepharitis
- Conjunctivitis
- Rash
- Lack of production of tear fluid
- Tear fluid contains electrolytes, enzymes, lipid, surfactant, pH = 7.4
- Eye feels dry and gritty, more prone to infection
- Artificial tear fluid
- Examination of the corneal surface
- Diagnosis for imperfections
The Corneal Surface can be Examined using Fluorescein and Rose Bengal. What are the roles of these?
- Fluorescein
- Demonstrates defects in the epithelial layer
- Rose Bengal
- Demonstrates dead or degenerating epithelial cells
What is Age-related macular degeneration treated with?
- Treated with antibodies against vascular endothelial growth factor (ranibizumab)
- Important cytokine for development of blood vessels
What are general points when counselling about the application of the products?
- Avoid contaminating the container
- Perform in front of a mirror
- One or two drops
- About 5-10mm of ointment
- May apply genetle pressure with finger to reduce drainage
- Ointments can blur the patient’s vision
- Use of a cotton bud
For topical applied drug the barriers that affect the penetration are?
- Stromal tissues of the cornea and sclera
- Cornea epithlium and endothelium
- Outer and inner blood-retinal barriers
- Internal limiting membrane on the vitreoretinal interface
- Drainage of the instilled solution
- Lacrimation and tear turnover
- Metabolism and binding by the lacrimal proteins
- Drainage via the nasolacrimal system
What are the 2 routes of Applied Product?
- Drainage
- Absorption
- Through cornea
- Into surrounding tissue
What is the Fate of the Applied Product?
- Application of product
- Precorneal drug pool
- Tear fluid washes it
- Some goes to conjuctiva or cornea
- Some gets drained - nasolacrimal drainage
How are the Anterior and Posterior Chambers Accessed?
- Requires transport across the cornea
What Factors Influence the Residence Time in Contact with Tissue?
- Flow of Tear Fluid
- Viscosity
- Volume of Product Applied
What Factors Influence the Residence Time in Contact with Tissue?
Flow of Tear Fluid
- Normally about 15% of total volume per min
- Presence of irritation
- Osmotic pressure of product
- pH and buffering capacity of the product
- Temperature
- Movement of eye lids
What Factors Influence the Residence Time in Contact with Tissue?
Volume of Product Applied
- Capacity of conjunctival sac = 30mcL
- 1 or 2 drops only (50-100mcL)
- > 2 drops may cause noticeable systemic effects
- Ideal volume would be 10mcL
What Factors need to be Considered when Formulating Eye Drops?
- Sterility
- Minimisation of Contamination during use
- Minimising contamination - multiple use
- Chemical instability - hydrolysis, epimerisation, oxidation
- Retention of product within the eye - viscosity
- Acceptability for patient - clarity
- Packaging
Factors need to be Considered when Formulating Eye Drops
- Sterility
- When is this a risk?
- Sources of contamination?
- How is sterility achieved?
- Risk to user of non-sterile product
- Sources of contamination
- Raw materials
- Equipment
- Manufacturing personnel
- Achieved by
- Autoclaving
- Filtration
- Dry heat e.g. for ointments
- Ionising radiation e.g. for ointments
- Any other method proven by manufacturer
Factors need to be Considered when Formulating Eye Drops
- Minimasation of Contamination During Use
- Risk of Contamination during use
- Reduction in risk achieved by
- Risk of Contamination during use
- Multiple-use vs single-use
- Contamination by user
- Reduction in risk achieved by
- Addition of a microbiological preservative
- Instructions for discarding the product
- Single use?
- One month after opening?
- Minimal risk with ointments
Factors need to be Considered when Formulating Eye Drops
Minimasation of Contamination - Multiple Use
- Microbiological Preservatives Characteristics?
- Bacteriostatic
- Low toxicity
- Compatible with other components
- Chemically-stable
- Specified by APF
Factors need to be Considered when Formulating Eye Drops
- Chemical Instability may result from?
- Hydrolysis
- Oxidation
- Epimerisation
- Precipitation
Factors need to be Considered when Formulating Eye Drops
- Chemical Instability - Hydrolysis, Epimerisation may be minimised by what?
- Adjustment of pH
- Use a non-aqueous solvent
- Reconstitution of unstable active with eye drop base solution
- Suspension (reduced % of total drug in solution)
Factors need to be Considered when Formulating Eye Drops
- Chemical Instability - Oxidation may be minimised by what?
- Adjustment of pH
- Addition of an antioxidant
- Removal of potential catalyst
- Appropriate storage
Factors need to be Considered when Formulating Eye Drops
- Retention of product within the eye - viscosity may be enhanced by?
- Addition of a polymer
- May leave a dry film
Factors need to be Considered when Formulating Eye Drops
- Acceptability for patient - clarity
- Necessity for removal of particles
- Discomfit
- Abrasion to cornea
- Potential for infection
- Number minimised by
- Filtration
- 0.45 or 0.8mcm filter
- Suspensions
- Control over particle size
- Filtration
Factors need to be Considered when Formulating Eye Drops
Packaging
- Amber glass hexagonal ribbed bottle and glass dropper
- Polymeric containers
- Opaque low-density polyethylene bottle with nozzle
- Harder cap
- Greater risk of adsorption
- Permeation of volatile components
- Sterilised with ethylene oxide or radiation
- Multiple and single dose
