Ophthalmic Dosage Forms Flashcards
Definition of Ophthalmics
Sterile products for instillation into the eye. Can be solutions, suspensions, ointments or ophthalmic inserts
Normal tear volume
7ul
Volume accommodated without spillage
30ul
After blinking, residual volume
10ul
Commercial eye drops volume
50ul
Optimal volume to administer for ophthalmics
5-10ul
Factors lowering bioavailability
- Optimal volume of eye drops to administer - currently: optimal volume to administer is 5-10ul but commercial eye drops volume is 50 ul; ideally: high concentration/low volumes
- Absorption primarily through the cornea - cornea structure: lipid-rich epithelium layer (outer), lipid-poor stroma layer, lipid-rich endothelium layer (inner)
- Loss of drug: overflow and spillage; enzymatic degradation (lysosomes) and protein binding; removal by the naso-lacriminal apparatus - take place when reflex tearing causes volume to exceed 7-10ul, eventually goes to GI tract: potential systemic effects, salty/bitter taste; superficial adsorption by drug through the conjunctiva -> rapid removal by peripheral blood vessels
Administration considerations
- the ophthalmic formulation delivers the drug: on the eye; into the eye; onto the conjunctiva
- transcorneal transport is not an effective process. only 1/10 of a dose penetrates into the eye
- to optimize ocular drug delivery systems, the following characteristics are required:
1. a good corneal penetration
2. a prolonged contact time with the corneal epithelium -> more drug absorption
3. a simplicity of instillation for the patient -> design of the eye drop and and dropper
4. a non-irritative and comfortable form. should not provoke lacrymation and reflex blinking
Ophthalmic dosage forms
- solutions
- suspensions
- ointments
- ophthalmic inserts
- biodegradable drug delivery (BDD)
Requirements for ophthalmic solutions
- uniformity: all ingredients are in solution
- sterility: autoclave at 121C or use bacterial filters; preservatives
- buffers and pH: ideally formulate at pH 7.4
- viscosity and thickening agents: consider lacrimal drainage
- ocular bioavailability
- isotonicity value - osmotic pressure must be similar to that of the tears; tonicity limits for eye preparations 0.6 - 2% NaCl or its osmotic equivalent
Manufacturing technique for ophthalmic solutions
- Dissolve drug and all or part of excipients
- Sterilize by heat or membrane filtration
- If required, add the other sterilized excipients
- Bring to volume with sterile water
What are ophthalmic suspensions
Dispersions of insoluble drugs using suspending agents.
Optimum particle size (<10um) to facilitate dissolution and prevent irritation.
Solid particles will dissolve to replenish the absorbed drug, increasing contact time and duration of action
Manufacturing technique for ophthalmic suspensions
- Add the sterilized solid to the sterilized solution
- the solid is sterilized with heat, ethylene oxide, or aseptic recrystallization
(particle size control: <10um)
What are ophthalmic ointments
Drug released is a function of concentration, diffusivity and solubility in the base.
Advantage: longer contact time -> greater bioavailability
Manufacturing techniques for ophthalmic ointments
- Place the sterilized, filtered and molten base in a sterile, heated kettle
- Add sterilized drug and excipients aseptically
- Mill the melt to disperse insoluble components
What are ocular inserts
They are placed in the cul-de-sac between the eyeball and the eyelid (e.g. ocusert - non-eroding device designed to deliver pilocarpine for several drugs in the treatment of glaucoma) ; some are designed to dissolve in tear fluid (e.g. Lacrisert used to treat moderate to severe dry eye syndrome)
Biggest disadvantage: tendency to float on the eyeball
What are biodegradable drug delivery
Controlled intraocular delivery that assures efficient delivery of medication to treat disease inside the eye.
Designed to provide continuous, controlled release drug therapy directly to the targeted site for a period from days to several years.
Placed in the eye at the time of elective surgery
Dissolve as they release drug
Formulation factors to consider
- General: sterilization - laminar flow hood using aseptic techniques, sterility is an absolute requirement, vehicle - generally sterile isotonic solutions, extemporaneous compounding is rare
- Solution pH: pH of blood and tear is 7.4 -> pH range of solutions is maintained by buffer at 6.5 - 8.5 to prevent corneal damage as having pH 7.4 may not be possible considering solubility, stability or therapeutic activity
- Solution buffers: needed for adjusting and maintaining the pH of the solution for optimal pH
- Iso-osmoticity and isotonicity: NaCl equivalence (E) is used to measure the osmotic effect of solutions - blood and tears are iso-osmotic with 0.9% solution of NaCl; range of tonicities allowed from 0.6-1.8% NaCl solution
- Preservatives: added to prevent bacterial contamination (e.g. benzalkonium chloride 0.013%, chlorobutanol 0.5%, benzethonium chloride 0.01%)
- Antioxidants (e.g. EDTA-not often used in ophthalmic formulations due to low water solubility, sodium bisulfite, sodium metabisulfite, thiourea)
- Viscosity and thickening agents - more residence time (e.g. cellulose derivative, polyvinyl alcohol)
Packing of ophthalmic dosage forms
- Easy administration and sterility maintenance
- Packaged in low density polyethylene plastic with a fixed, built-in dropper to release medicine when in an inverted position
- Protect from light and tightly closed
- Stored at room temp. between 15 - 30C
- An ocumeter ensures sterility of the drops when in a multi dose container
- May require refrigeration to extend shelf life
Classification for contact lenses
- Soft - made from HEMA, cover the entire cornea, daily wear and extended wear
- Hard - made from PMMA, cover part of the cornea, float not he tear layer overlying the cornea
- Rigid gas permeable (RGP) lenses - oxygen permeable, durable and easy to handle
