ocular delivery Flashcards
Ocular barriers in topical drug delivery
Poor permeability of the cornea
Tear reflex
Nasolacrimal drainage
Blinking
Non-corneal absorption
corneal epithelium = impermeable
The corneal epithelium is a hydrophobic tissue and contributes 90 % of the barrier to hydrophilic drugs and 10 % to hydrophobic drugs;
The stroma is hydrophilic tissue (70-80 % is water; 20-25 % is collagen, proteins and mucopolysaccharides). It is the main barrier to extremely hydrophobic drugs;
There are significant levels of various enzymes (esterases, peptidases, proteases) in the ocular tissues including cornea. Many ocularly applied drugs are metabolised during or after absorption.
what are non-corneal absorption
Penetration across conjunctiva and underlying sclera into vitreous humour;
This route is important for hydrophilic drugs and large molecules such as insulin;
Conjuctival permeability of hydrophilic drugs is typically one order of magnitude greater than their corneal permeability;
Sclera is also more permeable than cornea.
what are approaches to optimise topical ocular drug delivery
- Proper placement of the eyedrops
A drop is placed in the inferior cul-de-sac by gently pulling the lower lid away from the globe and creating a pouch to receive the drop. After gently lifting the lid to touch the globe, a small amount of liquid is entrapped in the inferior conjunctival sac, where it may be retained up to twice as long as when it is simply dropped over the superior sclera. - Reducing the instilled volume of an eyedrop
- Optimal volume for instilled eye-drops is 8-15 L;
- Typical volumes delivered by commercial eyedroppers are in the range of 35-56 L;
- Only small proportion of the eye-drop can be retained by the eye. - Formulation approaches
Modify integrity of the corneal epithelium transiently (exposing the eye to compounds such as chelating agents and surfactants. However it has hardly been explored due to the sensitivity of this particular tissue).
Modify the chemical structure of the drug (pro-drug approach)
what is lantonoprost
use
a medication administered into the eyes to control the progression of glaucoma or ocular hypertension by reducing intraocular pressure.
inactive until it is hydrolysed by esterases in the cornea - it is a prodrug
what are Formulation approaches to improve precorneal retention
Viscous systems (polyvinyl alcohol, hydroxyethylcellulose)
Mucoadhesives (Carbopols or Carbomers)
Phase transition systems (in situ gelling systems)
- changes in pH (cellulose acetate phtalate and Carbomer solutions will form gel when in contact with the tear fluid pH 7.4);
- changes in temperature (Pluronics)
- Changes in ions composition (gellan gum, sodium alginate)
how are contact lenses classified?
Contact lenses are classified as either hard or soft contact lenses according to their modulus of elasticity. Soft contact lens are either hydrogels or silicone-based elastomers.
hard lenses have smaller diameter
These devices were effectively glass shells which covered the whole of the front of the eye; they were produced using rabbit and cadaver eyes as moulds;
what are problems with medicated contact lenses
Problems
Burst release profiles
Poor loading capacity for many drugs
what are the Approaches to improve the performance of medicated contact lenses
- Multilayered lenses
Zero-order release kinetics;
Therapeutically relevant concentrations for 1 month - Drug-loaded nanoparticles within the lenses
what are ocular inserts
use
advice
Ocusert (Alza Corporation, USA) is an insoluble ophthalmic insert classified in the group of diffusional systems. It consists of a central reservoir of drug (e.g. pilocarpine) enclosed between two semi-permeable membranes which allow the drug to diffuse from the reservoir at a precisely determined rate for a period of 7 days;
Prolonged reduction in intraocular pressure was achieved with a single Ocusert in patients with hypertensive open-angle glaucoma.
Because of the insolubility of the Ocusert device, it must be removed after use. The inserts were well tolerated but after prolonged wear tended to swell and partially fragment.
It is recommended that they not be worn for more than 12 h, despite the potential for prolonged release of several days
what is mydriasert
Each ophthalmic insert contains 0.28 mg of tropicamide and 5.4 mg of phenylephrine hydrochloride
Excipients: ammonio-methacrylate
copolymer (Type A), polyacrylate dispersion, glycerol dibehenate and ethylcellulose
- causes pupil dilation
Intraocular drug delivery
Intravitreal injections
Liposomes
Have potential to increase the activity and prolong the residence of the drug in the eye. Liposomes can also reduce intraocular toxicity of certain potent drugs.
Microparticulates and nanoparticles
Intraocular devices (implants)
Iontophoresis
what is Intravitreal injections
halflife
Direct intravitreal injection of drugs into the vitreous cavity is employed to achieve higher drug concentrations in the vitreous and the retina;
The half-life of drugs in the vitreous is relatively short;
Repeated injections are needed to maintain drug concentrations at an effective therapeutic level over a certain period of time
Repeated intravitreal injections results in patient discomfort and may lead to complications such as vitreous hemorrhage, infection, and lens or retinal injury
OZURDEX
use
OZURDEX® is a sustained-release, biodegradable implant containing the corticosteroid dexamethasone;
One implant contains 700 mcg
of dexamethasone;
The implant is approximately 0.46 mm
in diameter and 6 mm in length;
It is indicated for the treatment of adult
patients with visual impairment due
to diabetic macular oedema inflammation of
the posterior segment of the eye
presenting as non-infectious uveitis;
